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公开(公告)号：US20200181280A1
公开(公告)日：2020-06-11
申请号：US16429829
申请日：2019-06-03
申请人： The United States of America, as represented by the Secretary,Department of Health and Human Service , Hoffmann-La Roche Inc.
发明人： Ira H. Pastan , Ronit Mazor , Masanori Onda , Byungkook Lee , Gerhard Niederfellner , Sabine Imhof-Jung , Ulrich Brinkmann , Werner Scheuer , Guy Georges
IPC分类号： C07K16/30 , C07K14/21 , C07K16/12 , C07K16/40 , A61K31/337 , A61K47/68 , A61K39/395
摘要： The invention provides a Pseudomonas exotoxin A (PE) comprising an amino acid sequence having a substitution of one or more B-cell and/or T-cell epitopes. The invention further provides related chimeric molecules, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions. Methods of treating or preventing cancer in a mammal, methods of inhibiting the growth of a target cell, methods of producing the PE, and methods of producing the chimeric molecule are further provided by the invention.
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公开(公告)号：US09492564B2
公开(公告)日：2016-11-15
申请号：US14270836
申请日：2014-05-06
申请人： Duke University , The United States of America as represented by the Secretary, Department of Health and Human Service
发明人： Darell Bigner , Chien-Tsun Kuan , Ira H. Pastan , Charles Peagram
IPC分类号： A61K39/395 , A61K47/48 , C07K16/28 , A61K39/00
CPC分类号： C07K16/2863 , A61K38/00 , A61K39/39558 , A61K47/6829 , A61K47/6849 , A61K2039/505 , A61K2039/545 , C07K14/21 , C07K2317/56 , C07K2317/565 , C07K2317/622 , C07K2317/624 , C07K2317/92 , C07K2319/04 , C07K2319/55
摘要： We tested the in vitro and in vivo efficacy of a recombinant bispecific immunotoxin that recognizes both EGFRwt and tumor-specific EGFRvIII receptors. A single chain antibody was cloned from a hybridoma and fused to toxin, carrying a C-terminal peptide which increases retention within cells. The binding affinity and specificity of the recombinant bispecific immunotoxin for the EGFRwt and the EGFRvIII proteins was measured. In vitro cytotoxicity was measured. In vivo activity of the recombinant bispecific immunotoxin was evaluated in subcutaneous models and compared to that of an established monospecific immunotoxin. In our preclinical studies, the bispecific recombinant immunotoxin, exhibited significant potential for treating brain tumors.
摘要翻译： 我们测试了识别EGFR重组和肿瘤特异性EGFRvIII受体的重组双特异性免疫毒素的体外和体内功效。 从杂交瘤中克隆单链抗体并与毒素融合，携带增加细胞内保留的C-末端肽。 测量了重组双特异性免疫毒素对EGFRwt和EGFRvIII蛋白的结合亲和力和特异性。 测量体外细胞毒性。 在皮下模型中评估重组双特异性免疫毒素的体内活性，并与已建立的单特异性免疫毒素的体内活性进行比较。 在我们的临床前研究中，双特异性重组免疫毒素显示出显着的治疗脑肿瘤的潜力。
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公开(公告)号：US20200247901A1
公开(公告)日：2020-08-06
申请号：US16613971
申请日：2018-05-17
申请人： The United States of America, as represented by the Secretary,Department of Health and Human Service
发明人： Ira H. Pastan , Masanori Onda , Tapan Bera , Mitchell Ho
IPC分类号： C07K16/30 , A61K47/68 , G01N33/574 , A61P35/00
摘要： Polypeptides and proteins that specifically bind to and immunologically recognize human mesothelin582-598 (IP-NGYLVLDLSMQEALS) (SEQ ID NO: 1) are disclosed. Anti-mesothelin binding moieties, nucleic acids, recombinant expression vectors, host cells, populations of cells, pharmaceutical compositions, and conjugates relating to the polypeptides and proteins are disclosed. Methods of reducing mesothelin shed from cell membranes, methods of reducing the activity of TNFα converting enzyme, methods of detecting the presence of cancer, and methods of treating or preventing cancer are also disclosed.
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公开(公告)号：US20180318435A1
公开(公告)日：2018-11-08
申请号：US15773687
申请日：2016-11-10
申请人： The United States of America,as represented by the Secretary, Department of Health and Human Service , Sanford Research
发明人： Ira H. Pastan , Tapan Bera , Satoshi Nagata , Tomoko Ise , Yasuhiro Abe
CPC分类号： A61K47/6415 , A61K39/00 , A61K47/6425 , A61K2039/505 , C07K16/2878 , C07K2319/03
摘要： Polypeptides and proteins that specifically bind to and immunologically recognize B-Cell Maturation Antigen (BCMA) are disclosed. Chimeric antigen receptors (CARs), anti-BCMA binding moieties, nucleic acids, recombinant expression vectors, host cells, populations of cells, pharmaceutical compositions, and conjugates relating to the polypeptides and proteins are also disclosed. Methods of detecting the presence of cancer and methods of treating or preventing cancer are also disclosed.
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公开(公告)号：US20210024648A1
公开(公告)日：2021-01-28
申请号：US16785911
申请日：2020-02-10
申请人： The United States of America, as represented by the Secretary, Department of Health and Human Servic , Hoffmann-La Roche Inc.
发明人： Ira H. Pastan , Ronit Mazor , Masanori Onda , Byungkook Lee , Gerhard Niederfellne , Sabine Imhof-Jung , Ulrich Brinkmann , Guy Georges
IPC分类号： C07K16/30 , C07K16/12 , A61K47/68 , A61K39/395 , A61K31/337 , C07K16/40 , C07K14/21
摘要： The invention provides a Pseudomonas exotoxin A (PE) comprising an amino acid sequence having a substitution of one or more B-cell and/or T-cell epitopes. The invention further provides related chimeric molecules, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions. Methods of treating or preventing cancer in a mammal, methods of inhibiting the growth of a target cell, methods of producing the PE, and methods of producing the chimeric molecule are further provided by the invention.
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公开(公告)号：US20170051072A1
公开(公告)日：2017-02-23
申请号：US15191392
申请日：2016-06-23
申请人： The United States of America, as represented by the Secretary, Department of Health and Human Serv , Hoffmann-La Roche Inc.
发明人： Ira H. Pastan , Ronit Mazor , Masanori Onda , Byungkook Lee , Gerhard Niederfellner , Sabine Imhof-Jung , Ulrich Brinkmann , Werner Scheuer , Guy Georges
CPC分类号： C07K16/30 , A61K31/337 , A61K38/00 , A61K39/39558 , A61K47/6803 , A61K47/6829 , A61K47/6851 , A61K47/6859 , A61K47/6871 , A61K2039/505 , C07K14/21 , C07K16/1214 , C07K16/303 , C07K16/40 , C07K2317/24 , C07K2317/55 , C07K2317/624 , C07K2317/73 , C07K2317/92 , C07K2317/94 , C07K2319/30 , C07K2319/33 , C07K2319/50 , C07K2319/55 , A61K2300/00
摘要： The invention provides a Pseudomonas exotoxin A (PE) comprising an amino acid sequence having a substitution of one or more B-cell and/or T-cell epitopes. The invention further provides related chimeric molecules, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions. Methods of treating or preventing cancer in a mammal, methods of inhibiting the growth of a target cell, methods of producing the PE, and methods of producing the chimeric molecule are further provided by the invention.
摘要翻译： 本发明提供了包含具有一个或多个B细胞和/或T细胞表位取代的氨基酸序列的假单胞菌外毒素A（PE）。 本发明还提供相关的嵌合分子以及相关的核酸，重组表达载体，宿主细胞，细胞群和药物组合物。 治疗或预防哺乳动物癌症的方法，抑制靶细胞生长的方法，生产PE的方法和制备嵌合分子的方法进一步由本发明提供。
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公开(公告)号：US09388222B2
公开(公告)日：2016-07-12
申请号：US14505590
申请日：2014-10-03
申请人： The United States of America, as represented by the Secretary, Department of Health and Human Services , Hoffmann-La Roche Inc.
发明人： Ira H. Pastan , Ronit Mazor , Masanori Onda , Byungkook Lee , Gerhard Niederfellner , Sabine Imhof-Jung , Ulrich Brinkmann , Guy Georges
CPC分类号： C07K16/30 , A61K31/337 , A61K38/00 , A61K39/39558 , A61K47/6803 , A61K47/6829 , A61K47/6851 , A61K47/6859 , A61K47/6871 , A61K2039/505 , C07K14/21 , C07K16/1214 , C07K16/303 , C07K16/40 , C07K2317/24 , C07K2317/55 , C07K2317/624 , C07K2317/73 , C07K2317/92 , C07K2317/94 , C07K2319/30 , C07K2319/33 , C07K2319/50 , C07K2319/55 , A61K2300/00
摘要： The invention provides a Pseudomonas exotoxin A (PE) comprising an amino acid sequence having a substitution of one or more B-cell and/or T-cell epitopes. The invention further provides related chimeric molecules, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions. Methods of treating or preventing cancer in a mammal, methods of inhibiting the growth of a target cell, methods of producing the PE, and methods of producing the chimeric molecule are further provided by the invention.
摘要翻译： 本发明提供了包含具有一个或多个B细胞和/或T细胞表位取代的氨基酸序列的假单胞菌外毒素A（PE）。 本发明还提供相关的嵌合分子以及相关的核酸，重组表达载体，宿主细胞，细胞群和药物组合物。 治疗或预防哺乳动物癌症的方法，抑制靶细胞生长的方法，生产PE的方法和制备嵌合分子的方法进一步由本发明提供。
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公开(公告)号：US20150099707A1
公开(公告)日：2015-04-09
申请号：US14505590
申请日：2014-10-03
申请人： The United States of America, as represented by the Secretary, Department of Health and Human Serv , Hoffmann-La Roche Inc.
发明人： Ira H. Pastan , Ronit Mazor , Masanori Onda , Byungkook Lee , Gerhard Niederfellner , Sabine Imhof-Jung , Ulrich Brinkmann , Werner Scheuer , Guy Georges
CPC分类号： C07K16/30 , A61K31/337 , A61K38/00 , A61K39/39558 , A61K47/6803 , A61K47/6829 , A61K47/6851 , A61K47/6859 , A61K47/6871 , A61K2039/505 , C07K14/21 , C07K16/1214 , C07K16/303 , C07K16/40 , C07K2317/24 , C07K2317/55 , C07K2317/624 , C07K2317/73 , C07K2317/92 , C07K2317/94 , C07K2319/30 , C07K2319/33 , C07K2319/50 , C07K2319/55 , A61K2300/00
摘要： The invention provides a Pseudomonas exotoxin A (PE) comprising an amino acid sequence having a substitution of one or more B-cell and/or T-cell epitopes. The invention further provides related chimeric molecules, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions. Methods of treating or preventing cancer in a mammal, methods of inhibiting the growth of a target cell, methods of producing the PE, and methods of producing the chimeric molecule are further provided by the invention.
摘要翻译： 本发明提供了包含具有一个或多个B细胞和/或T细胞表位取代的氨基酸序列的假单胞菌外毒素A（PE）。 本发明还提供相关的嵌合分子以及相关的核酸，重组表达载体，宿主细胞，细胞群和药物组合物。 治疗或预防哺乳动物癌症的方法，抑制靶细胞生长的方法，生产PE的方法和制备嵌合分子的方法进一步由本发明提供。
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