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1. 发明授权

US4962188A Recombinant ricin toxin A chain conjugates 失效
标题翻译：重组蓖麻毒素A链缀合物
公开(公告)号：US4962188A
公开(公告)日：1990-10-09
申请号：US913357
申请日：1986-09-30
申请人： Arthur E. Frankel
发明人： Arthur E. Frankel
IPC分类号： A61K38/00 , A61K47/48 , C07K16/30
CPC分类号： C07K16/30 , A61K47/48638 , A61K38/00 , Y10S424/804 , Y10S424/807 , Y10S514/885 , Y10S530/808 , Y10S530/861 , Y10S530/864
摘要： Conjugates comprising recombinant ricin toxin A chain and a binding moiety which may be an antigen binding portion selected from the group consisting of Fab, Fab' and F(ab').sub.2 fragments of monoclonal or polyclonal antibodies, hormones, lectins or other compounds that are recognized by cell receptors, are described and claimed.
摘要翻译：包含重组蓖麻毒素A链和结合部分的缀合物，所述结合部分可以是选自单克隆或多克隆抗体，激素，凝集素或其它化合物的Fab，Fab'和F（ab'）2片段的抗原结合部分，由细胞受体识别，被描述和要求保护。

2. 发明授权

US4803169A Assay for human breast cancer 失效
标题翻译：人乳腺癌检测
公开(公告)号：US4803169A
公开(公告)日：1989-02-07
申请号：US826477
申请日：1986-02-05
申请人： Peter S. Linsley , Vincent W. Ochs , Diane Horn , Joseph P. Brown , David B. Ring , Arthur E. Frankel
发明人： Peter S. Linsley , Vincent W. Ochs , Diane Horn , Joseph P. Brown , David B. Ring , Arthur E. Frankel
IPC分类号： C12N15/00 , C12N15/02 , C12P21/00 , C12P21/08 , G01N33/574 , G01N33/577
CPC分类号： G01N33/57415 , Y10S436/813
摘要： Methods are disclosed for detecting, staging and monitoring breast cancer. The methods involve determining the amount of certain antigens, designated W1 and W9, in serum via quantitative immunoassays using anti-W1 or anti-W9 monoclonal antibodies. The amount detected is compared with amounts of the antigen found in normal sera, sera from breast cancer patients of predetermined stage, or other samples of the patient's own serum, depending upon the purpose of the assay.
摘要翻译：公开了用于检测，分期和监测乳腺癌的方法。所述方法包括使用抗-W1或抗-W9单克隆抗体通过定量免疫测定来测定血清中某些抗原（称为W1和W9）的量。根据测定的目的，将检测到的量与在正常血清，预定阶段的乳腺癌患者的血清或患者自身血清的其他样品中发现的抗原的量进行比较。

3. 发明申请

US20120232010A1 Compositions and Methods for Treating Bladder Cancer 有权
标题翻译：治疗膀胱癌的组合物和方法
公开(公告)号：US20120232010A1
公开(公告)日：2012-09-13
申请号：US13502132
申请日：2010-10-14
申请人： Thomas Flaig , Arthur E. Frankel , Andrew Thorburn , L.Michael Glode , Jung Hee Woo , David Neville
发明人： Thomas Flaig , Arthur E. Frankel , Andrew Thorburn , L.Michael Glode , Jung Hee Woo , David Neville
IPC分类号： A61K38/18 , C07K19/00 , A61P35/00
CPC分类号： C07K14/485 , A61K38/00 , A61K38/16 , A61K38/164 , A61K38/1808 , C07K14/34
摘要： The present invention provides methods and compositions for treating bladder cancer. In particular, the present invention provides a fusion protein comprising a toxin moiety that is linked to an epithelial growth factor (EGF) moiety. The toxin moiety and the EGF moiety can be linked optionally via a linker. Typically, the fusion protein is administered intravesically into the cancerous bladder.
摘要翻译：本发明提供了治疗膀胱癌的方法和组合物。特别地，本发明提供了包含与上皮生长因子（EGF）部分连接的毒素部分的融合蛋白质。可以通过接头任选地连接毒素部分和EGF部分。通常，融合蛋白被膀胱内施用于癌性膀胱。

4. 发明申请

US20090232767A1 METHODS AND COMPOSITIONS BASED ON DIPHTHERIA TOXIN-INTERLEUKIN-3 CONJUGATES 有权
标题翻译：基于DIPHTHERIA TOXIN-INTERLEUKIN-3结合物的方法和组合物
公开(公告)号：US20090232767A1
公开(公告)日：2009-09-17
申请号：US12368048
申请日：2009-02-09
申请人： Arthur E. Frankel
发明人： Arthur E. Frankel
IPC分类号： A61K38/20 , A61P35/00
CPC分类号： C07K14/5403 , A61K35/14 , A61K35/28 , A61K38/00 , A61K38/164 , A61K38/202 , A61K47/642 , C07K14/34 , C07K2319/55 , Y10S514/885 , A61K2300/00
摘要： The present invention provides methods for inhibiting interleukin-3 receptor-expressing cells, and, in particular, inhibiting the growth of such cells by using a diphtheria toxin-human interleukin-3 conjugate (DT-IL3) that is toxic to cells expressing the interleukin-3 receptor. In preferred embodiments, the DT-IL3 conjugate is a fusion protein comprising amino acids 1-388 of diphtheria toxin fused via a peptide linker to full-length, human interleukin-3. In certain embodiments, the methods of the present invention relate to the administration of a DT-IL3 conjugate to inhibit the growth of cancer cells and/or cancer stem cells in humans, which cells express one or more subunits of the interleukin-3 receptor. Exemplary cells include myeloid leukemia cancer stem cells. In other embodiments, the methods of the present invention relate to ex vivo purging of bone marrow or peripheral blood to remove cells that express one or more subunits of the interleukin-3 receptor such that the purged bone marrow or peripheral blood is suitable, e.g., for autologous stem cell transplantation to restore hematopoietic function.
摘要翻译：本发明提供了抑制白细胞介素-3受体表达细胞的方法，特别是通过使用对表达白介素的细胞有毒性的白喉毒素 - 人白细胞介素-3缀合物（DT-IL3）来抑制这些细胞的生长 -3受体。在优选的实施方案中，DT-IL3缀合物是包含通过肽连接体融合到全长人白细胞介素-3的白喉毒素的氨基酸1-388的融合蛋白。在某些实施方案中，本发明的方法涉及施用DT-IL3缀合物以抑制人类癌细胞和/或癌干细胞的生长，所述细胞表达白细胞介素-3受体的一个或多个亚单位。示例性细胞包括骨髓性白血病癌症干细胞。在其它实施方案中，本发明的方法涉及骨髓或外周血的离体清除以去除表达白细胞介素-3受体的一个或多个亚基的细胞，使得被清除的骨髓或外周血适合，例如，用于自体干细胞移植以恢复造血功能。

5. 发明申请

US20080138313A1 Methods and compositions based on diphtheria toxin-interleukin-3 conjugates 有权
标题翻译：基于白喉毒素 - 白介素-3缀合物的方法和组合物
公开(公告)号：US20080138313A1
公开(公告)日：2008-06-12
申请号：US11899747
申请日：2007-09-07
申请人： Arthur E. Frankel
发明人： Arthur E. Frankel
IPC分类号： A61K45/00 , A01N1/02 , A01N63/00
CPC分类号： C07K14/5403 , A61K35/14 , A61K35/28 , A61K38/00 , A61K38/164 , A61K38/202 , A61K47/642 , C07K14/34 , C07K2319/55 , Y10S514/885 , A61K2300/00
摘要： The present invention provides methods for inhibiting interleukin-3 receptor-expressing cells, and, in particular, inhibiting the growth of such cells by using a diphtheria toxin-human interleukin-3 conjugate (DT-IL3) that is toxic to cells expressing the interleukin-3 receptor. In preferred embodiments, the DT-IL3 conjugate is a fusion protein comprising amino acids 1-388 of diphtheria toxin fused via a peptide linker to full-length, human interleukin-3. In certain embodiments, the methods of the present invention relate to the administration of a DT-IL3 conjugate to inhibit the growth of cancer cells and/or cancer stem cells in humans, which cells express one or more subunits of the interleukin-3 receptor. Exemplary cells include myeloid leukemia cancer stem cells. In other embodiments, the methods of the present invention relate to ex vivo purging of bone marrow or peripheral blood to remove cells that express one or more subunits of the interleukin-3 receptor such that the purged bone marrow or peripheral blood is suitable, e.g., for autologous stem cell transplantation to restore hematopoietic function.
摘要翻译：本发明提供抑制白细胞介素-3受体表达细胞的方法，特别是通过使用对表达白细胞介素的细胞有毒性的白喉毒素 - 人白细胞介素-3缀合物（DT-IL3）来抑制这些细胞的生长 -3受体。在优选的实施方案中，DT-IL3缀合物是包含通过肽连接体融合到全长人白细胞介素-3的白喉毒素的氨基酸1-388的融合蛋白。在某些实施方案中，本发明的方法涉及施用DT-IL3缀合物以抑制人类癌细胞和/或癌干细胞的生长，所述细胞表达白细胞介素-3受体的一个或多个亚单位。示例性细胞包括骨髓性白血病癌症干细胞。在其他实施方案中，本发明的方法涉及骨髓或外周血的离体清除以去除表达白介素-3受体的一个或多个亚基的细胞，使得被清除的骨髓或外周血适合，例如，用于自体干细胞移植以恢复造血功能。

6. 发明授权

US5667786A Method for treating tumors with a toxin 失效
标题翻译：用毒素治疗肿瘤的方法
公开(公告)号：US5667786A
公开(公告)日：1997-09-16
申请号：US486200
申请日：1995-06-07
申请人： Paul V. Lemley, Jr. , Arthur E. Frankel
发明人： Paul V. Lemley, Jr. , Arthur E. Frankel
IPC分类号： A61K38/00 , A61K38/16 , A61K39/00 , A61K39/07 , A61P35/00 , A61K39/02
CPC分类号： A61K38/164 , A61K38/168
摘要： A method for treating a tumor is provided, which comprises the steps of preliminarily immunizing a patient in need of antitumor treatment with a toxin or toxin surrogate vaccine in an amount which is effective to generate an immune response to the toxin in the patient, thereby providing systemic protection from the toxin to the patient, and subsequently administering the toxin to the patient in an amount which is effective to kill tumor cells. The toxin may be any suitable toxin, for example ricin, abrin, gelonin or diphtheria.
摘要翻译：提供了一种治疗肿瘤的方法，其包括以有效产生对患者的毒素的免疫应答的量，预先用毒素或毒素替代疫苗预防免疫需要抗肿瘤治疗的患者的步骤，由此提供从毒素到患者的全身保护，然后以有效杀死肿瘤细胞的量将毒素给予患者。毒素可以是任何合适的毒素，例如蓖麻毒素，相思豆毒素，白藜芦醇或白喉。

7. 发明授权

US6060066A Method for treating tumors with a toxin 失效
标题翻译：用毒素治疗肿瘤的方法
公开(公告)号：US6060066A
公开(公告)日：2000-05-09
申请号：US897090
申请日：1997-07-18
申请人： Paul V. Lemley, Jr. , Arthur E. Frankel
发明人： Paul V. Lemley, Jr. , Arthur E. Frankel
IPC分类号： A61K38/00 , A61K38/16 , A61K39/00 , A61K39/07 , A61P35/00 , A61K39/02
CPC分类号： A61K38/164 , A61K38/168
摘要： A method for treating a tumor is provided, which comprises the steps of preliminarily immunizing a patient in need of antitumor treatment with a toxin or toxin surrogate vaccine in an amount which is effective to generate an immune response to the toxin in the patient, thereby providing systemic protection from the toxin to the patient, and subsequently administering the toxin to the patient in an amount which is effective to kill tumor cells. The toxin may be any suitable toxin, for example ricin, abrin, gelonin or diphtheria.
摘要翻译：提供了一种治疗肿瘤的方法，其包括以有效产生对患者的毒素的免疫应答的量，预先用毒素或毒素替代疫苗预防免疫需要抗肿瘤治疗的患者的步骤，由此提供从毒素到患者的全身保护，然后以有效杀死肿瘤细胞的量将毒素给予患者。毒素可以是任何合适的毒素，例如蓖麻毒素，相思豆毒素，白藜芦醇或白喉。

8. 发明授权

US5169774A Monoclonal anti-human breast cancer antibodies 失效
标题翻译：单克隆抗人乳腺癌抗体
公开(公告)号：US5169774A
公开(公告)日：1992-12-08
申请号：US190778
申请日：1988-05-06
申请人： Arthur E. Frankel , David B. Ring , Walter Laird
发明人： Arthur E. Frankel , David B. Ring , Walter Laird
IPC分类号： A61K38/00 , C07K16/30
CPC分类号： C07K16/3015 , A61K38/00 , C07K2317/24 , C07K2317/622 , Y10S436/813 , Y10S530/808 , Y10S530/809 , Y10S530/864
摘要： Murine monoclonal antibodies, or fragments thereof, that bind selectively to human breast cancer cells, are IgGs or IgMs, and when conjugated to ricin A chain, exhibit a TCID 50% against at least one of MCF-7, CAMA-1, SKBR-3, or BT-20 cells of less than about 10 nM. Methods for diagnosing, monitoring, and treating human breast cancer with the antibodies or immunotoxins made therefrom are described.
摘要翻译：与人乳腺癌细胞结合选择性的鼠单克隆抗体或其片段是IgG或IgM，当与蓖麻毒蛋白A链结合时，其对MCF-7，CAMA-1，SKBR- 3或BT-20细胞小于约10nM。描述了用由其制备的抗体或免疫毒素来诊断，监测和治疗人乳腺癌的方法。

9. 发明授权

US4956453A Anti-human ovarian cancer immunotoxins and methods of use thereof 失效
标题翻译：抗人卵巢癌免疫毒素及其使用方法
公开(公告)号：US4956453A
公开(公告)日：1990-09-11
申请号：US69720
申请日：1987-07-06
申请人： Michael J. Bjorn , Arthur E. Frankel , Walter J. Laird , David B. Ring , Jeffrey L. Winkelhake
发明人： Michael J. Bjorn , Arthur E. Frankel , Walter J. Laird , David B. Ring , Jeffrey L. Winkelhake
IPC分类号： A61K38/00 , A61K47/48 , C07K16/30
CPC分类号： C07K16/30 , A61K47/48638 , A61K38/00 , Y10S424/804 , Y10S424/807 , Y10S514/885 , Y10S530/808 , Y10S530/861 , Y10S530/864 , Y10S530/866
摘要： Immunotoxins comprising a cytotoxic moiety and an antigen binding portion selected from the group consisting of Fab, Fab' and F(ab').sub.2 fragments of a monoclonal antibody, which binds to human ovarian cancer tissue, having one of the following capabilities are claimed: cytotoxic ID.sub.50 of about 10 nM or less against human ovarian cancer cells, retardation of human ovarian cancer tumor growth in mammals, or extension of survival of a mammal carrying a human ovarian cancer tumor. Antigens or epitopes to which the monoclonal antibodies bind are identified and characterize the immunotoxins. In a preferred embodiment an immunotoxin comprising at least an antigen binding portion of a monoclonal antibody, which binds to human transferrin receptor, but does not block binding of transferrin to the receptor, is described and claimed. Immunotoxin comprising the F(ab').sub.2 region of the antitransferrin monoclonal antibody are also claimed.Methods of killing human ovarian cancer cells, retarding the growth of human ovarian cancer tumors in mammals and extending the survial of mammals carrying human ovarian cancer tumors are claimed.
摘要翻译：要求具有下列能力之一的包含细胞毒素部分和选自Fab，Fab'和F（ab'）2结合部分的单克隆抗体结合人卵巢癌组织的抗原结合部分的免疫毒素：对人卵巢癌细胞约10nM或更少的细胞毒性ID50，哺乳动物中人卵巢癌肿瘤生长的延迟或携带人卵巢癌肿瘤的哺乳动物的存活的延长。识别单克隆抗体结合的抗原或表位，并表征免疫毒素。在优选的实施方案中，描述并要求保护包含至少结合人转铁蛋白受体但不阻断转铁蛋白与受体结合的单克隆抗体的抗原结合部分的免疫毒素。还要求保护包含抗转铁蛋白单克隆抗体的F（ab'）2区的免疫毒素。要求杀死人类卵巢癌细胞的方法，延缓哺乳动物中人卵巢癌肿瘤的生长并延长携带人卵巢癌肿瘤的哺乳动物的存活。

10. 发明授权

US08470307B2 Methods for treating acute myeloid leukemia with diphtheria toxin-interleukin-3 conjugates 有权
标题翻译：用白喉毒素 - 白介素-3缀合物治疗急性骨髓性白血病的方法
公开(公告)号：US08470307B2
公开(公告)日：2013-06-25
申请号：US12368048
申请日：2009-02-09
申请人： Arthur E. Frankel
发明人： Arthur E. Frankel
IPC分类号： A61K38/20
CPC分类号： C07K14/5403 , A61K35/14 , A61K35/28 , A61K38/00 , A61K38/164 , A61K38/202 , A61K47/642 , C07K14/34 , C07K2319/55 , Y10S514/885 , A61K2300/00
摘要： The present invention provides methods for inhibiting interleukin-3 receptor-expressing cells, and, in particular, inhibiting the growth of such cells by using a diphtheria toxin-human interleukin-3 conjugate (DT-IL3) that is toxic to cells expressing the interleukin-3 receptor. In preferred embodiments, the DT-IL3 conjugate is a fusion protein comprising amino acids 1-388 of diphtheria toxin fused via a peptide linker to full-length, human interleukin-3. In certain embodiments, the methods of the present invention relate to the administration of a DT-IL3 conjugate to inhibit the growth of cancer cells and/or cancer stem cells in humans, which cells express one or more subunits of the interleukin-3 receptor. Exemplary cells include myeloid leukemia cancer stem cells. In other embodiments, the methods of the present invention relate to ex vivo purging of bone marrow or peripheral blood to remove cells that express one or more subunits of the interleukin-3 receptor such that the purged bone marrow or peripheral blood is suitable, e.g., for autologous stem cell transplantation to restore hematopoietic function.
摘要翻译：本发明提供了抑制白细胞介素-3受体表达细胞的方法，特别是通过使用对表达白介素的细胞有毒性的白喉毒素 - 人白细胞介素-3缀合物（DT-IL3）来抑制这些细胞的生长 -3受体。在优选的实施方案中，DT-IL3缀合物是包含通过肽连接体融合到全长人白细胞介素-3的白喉毒素的氨基酸1-388的融合蛋白。在某些实施方案中，本发明的方法涉及施用DT-IL3缀合物以抑制人类癌细胞和/或癌干细胞的生长，所述细胞表达白细胞介素-3受体的一个或多个亚单位。示例性细胞包括骨髓性白血病癌症干细胞。在其他实施方案中，本发明的方法涉及骨髓或外周血的离体清除以去除表达白介素-3受体的一个或多个亚基的细胞，使得被清除的骨髓或外周血适合，例如，用于自体干细胞移植以恢复造血功能。

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