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1. 发明申请

US20140094417A1 PSEUDOMONAS EXOTOXIN A WITH LESS IMMUNOGENIC T CELL AND/OR B CELL EPITOPES 有权
标题翻译：具有较少免疫原性细胞和/或B细胞外膜的PSEUDOMONAS EXOTOXIN A
公开(公告)号：US20140094417A1
公开(公告)日：2014-04-03
申请号：US14123971
申请日：2012-06-07
申请人： Ira H. Pastan , Ronit Mazor , Masanori Onda , Aaron Vassall , Richard Beers , Jaime Eberle , Wenhai Liu
发明人： Ira H. Pastan , Ronit Mazor , Masanori Onda , Aaron Vassall , Richard Beers , Jaime Eberle , Wenhai Liu
IPC分类号： C07K14/21 , C07K16/28
CPC分类号： C07K14/21 , A61K38/00 , C07K16/2896 , C07K2319/33 , C07K2319/55
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。

2. 发明授权

US09346859B2 Pseudomonas exotoxin A with less immunogenic T cell and/or B cell epitopes 有权
标题翻译：具有较少免疫原性T细胞和/或B细胞表位的假单胞菌外毒素A
公开(公告)号：US09346859B2
公开(公告)日：2016-05-24
申请号：US14123971
申请日：2012-06-07
申请人： Ira H. Pastan , Ronit Mazor , Masanori Onda , Aaron Vassall , Richard Beers , Jaime Eberle , Wenhai Liu
发明人： Ira H. Pastan , Ronit Mazor , Masanori Onda , Aaron Vassall , Richard Beers , Jaime Eberle , Wenhai Liu
IPC分类号： A61K38/16 , A61P35/00 , C07K14/21 , C07K16/28 , A61K38/00
CPC分类号： C07K14/21 , A61K38/00 , C07K16/2896 , C07K2319/33 , C07K2319/55
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。

3. 发明授权

US08936792B2 Pseudomonas exotoxin a with reduced immunogenicity 有权
标题翻译：假单胞菌外毒素a具有降低的免疫原性
公开(公告)号：US08936792B2
公开(公告)日：2015-01-20
申请号：US13395422
申请日：2010-09-10
申请人： Ira H. Pastan , Richard Beers , Masanori Onda
发明人： Ira H. Pastan , Richard Beers , Masanori Onda
IPC分类号： A61K39/108 , C07K14/21 , A61K38/00
CPC分类号： C07K14/21 , A61K38/00
摘要： The present invention provides improved Pseudomonas Exotoxin A (PE) molecules with high cytotoxicity and reduced immunogenicity, compositions containing the improved (PE), and methods of use.
摘要翻译：本发明提供了具有高细胞毒性和降低的免疫原性的改进的假单胞菌外毒素A（PE）分子，含有改进的（PE）的组合物和使用方法。

4. 发明申请

US20120263674A1 PSEUDOMONAS EXOTOXIN A WITH REDUCED IMMUNOGENICITY 有权
标题翻译： PSEUDOMONAS EXOTOXIN A具有降低免疫原性
公开(公告)号：US20120263674A1
公开(公告)日：2012-10-18
申请号：US13395422
申请日：2010-09-10
申请人： Ira H. Pastan , Richard Beers , Masanori Onda
发明人： Ira H. Pastan , Richard Beers , Masanori Onda
IPC分类号： A61K39/395 , C12N9/96 , C12N15/62 , A61K38/45 , C12N15/54 , C12N9/10 , C12N5/09
CPC分类号： C07K14/21 , A61K38/00
摘要： The present invention provides improved Pseudomonas Exotoxin A (PE) molecules with high cytotoxicity and reduced immunogenicity, compositions containing the improved (PE), and methods of use.
摘要翻译：本发明提供了具有高细胞毒性和降低的免疫原性的改进的假单胞菌外毒素A（PE）分子，含有改进的（PE）的组合物和使用方法。

5. 发明授权

US07470775B2 Anti-CD30 stalk and anti-CD30 antibodies suitable for use in immunotoxins 失效
标题翻译：抗CD30茎和抗-CD30抗体适用于免疫毒素
公开(公告)号：US07470775B2
公开(公告)日：2008-12-30
申请号：US10516766
申请日：2003-06-09
申请人： Ira H. Pastan , Satoshi Nagata , Masanori Onda , Yoshito Numata , Kenneth Santora , Richard Beers , Robert Kreitman , Abhishek Sinha
发明人： Ira H. Pastan , Satoshi Nagata , Masanori Onda , Yoshito Numata , Kenneth Santora , Richard Beers , Robert Kreitman , Abhishek Sinha
IPC分类号： C12P21/08 , C07K16/00 , A61K39/395 , G01N33/574 , C07H21/04 , C12P21/04
CPC分类号： C07K16/2878 , A61K47/6829 , A61K47/6849 , A61K51/1027 , A61K2039/505 , C07K2317/622 , C07K2317/624 , C07K2317/734 , C07K2317/92 , C07K2319/00 , C07K2319/30
摘要： CD30 is a receptor expressed on cells of Hodgkin's disease and certain leukemias. The extracellular portion of CD30 is cleaved, releasing a form known as sCD30. The invention relates in part to the discovery that a residual, extracellular “stalk” of CD30 remains after cleavage of sCD30. The stalk provides an advantageous and previously unrecognized target for immunotoxins. The invention provides antibodies that bind to the CD30 stalk or to epitopes destroyed upon the cleavage of CD30 which results in the stalk. The invention further provides new anti-CD30 antibodies that form effective immunotoxins and are particularly suitable for making disulfide stabilized Fv (“dsFv”)-immunoconjugates. The dsFv immunoconjugates can be used as reagents to label CD30-expressing cancer cells or to inhibit the growth of CD30-expressing cancer cells. Moreover, the invention provides anti-CD30 antibodies that activate complement-dependent cytotoxicity.
摘要翻译： CD30是在霍奇金病和某些白血病细胞上表达的受体。 CD30的细胞外部分被切割，释放出称为sCD30的形式。本发明部分地涉及在sCD30切割后残留的CD30的残留的细胞外“茎”的发现。茎为免疫毒素提供了有利且以前未被认识的靶标。本发明提供了结合CD30茎或在导致茎的CD30切割时被破坏的表位的抗体。本发明进一步提供形成有效免疫毒素的新抗CD30抗体，特别适用于制备二硫键稳定的Fv（“dsFv”） - 免疫偶联物。 dsFv免疫偶联物可用作标记表达CD30的癌细胞的试剂或抑制表达CD30的癌细胞的生长。此外，本发明提供了激活补体依赖性细胞毒性的抗-CD30抗体。

6. 发明申请

US20140154248A1 RECOMBINANT IMMUNOTOXIN TARGETING MESOTHELIN 审中-公开
标题翻译：重组免疫抑制剂MESOTHELIN
公开(公告)号：US20140154248A1
公开(公告)日：2014-06-05
申请号：US14115131
申请日：2012-05-04
申请人： Ira H. Pastan , John Weldon , Richard Beers
发明人： Ira H. Pastan , John Weldon , Richard Beers
IPC分类号： C07K16/30 , C07K14/21
摘要： Mesothelin is a differentiation antigen present on the surface of ovarian cancers, mesotheliomas and several other types of human cancers. Because among normal tissues, mesothelin is only present on mesothelial cells, it represents a good target for antibody mediated delivery of cytotoxic agents. The present invention is directed to improved recombinant immunotoxins comprising anti-mesothelin antibodies, including Fv molecules with particularly high affinity for mesothelin, and a Pseudomonas Exotoxin moiety which has been modified to reduce its immunogenicity and protease sensitivity and providing a better cytotoxicity for cells which express mesothelin. The RITs are well-suited for the treatment of cancers of the ovary, stomach, squamous cells, mesotheliomas and other malignant cells expressing mesothelin.
摘要翻译：间皮素是存在于卵巢癌，间皮瘤和其他几种人类癌症表面的分化抗原。因为在正常组织中，间皮素仅存在于间皮细胞上，它代表抗体介导的细胞毒性剂递送的良好靶标。本发明涉及包含抗间皮素抗体的改良的重组免疫毒素，包括对间皮素具有特别高的亲和力的Fv分子，以及经修饰以降低其免疫原性和蛋白酶敏感性并为表达的细胞提供更好的细胞毒性的假单胞菌外毒素部分间皮素 RITs适用于治疗卵巢癌，胃癌，鳞状细胞癌，间皮瘤等表达间皮素的恶性细胞癌。

7. 发明申请

US20120258106A1 MUTATED ANTI-CD22 ANTIBODIES WITH INCREASED AFFINITY TO CD22-EXPRESSING LEUKEMIA CELLS 有权
标题翻译：具有增加CD22表达LEUKEMIA细胞的亲和力的突变型抗CD22抗体
公开(公告)号：US20120258106A1
公开(公告)日：2012-10-11
申请号：US13438725
申请日：2012-04-03
申请人： Ira H Pastan , Giuliana Salvatore , Richard Beers , Robert J. Kreitman
发明人： Ira H Pastan , Giuliana Salvatore , Richard Beers , Robert J. Kreitman
IPC分类号： C07K16/28 , C12N5/09 , A61P35/02 , A61K39/395 , A61P35/00 , G01N33/574 , C07K19/00
CPC分类号： C07K16/2803 , A61K47/6829 , A61K47/6849 , A61K47/6875 , A61K2039/505 , C07K2317/24 , C07K2317/565 , C07K2317/622 , C07K2317/624
摘要： Recombinant immunotoxins are fusion proteins composed of the Fv domains of antibodies fused to bacterial or plant toxins. RFB4 (Fv)-PE38 is an immunotoxin that targets CD22 expressed on B cells and B cell malignancies. The present invention provides antibodies and antibody fragments that have improved ability to bind the CD22 antigen of B cells and B cell malignancies compared to RFB4. Immunotoxins made with the antibodies and antibody fragments of the invention have improved cytotoxicity to CD22-expressing cancer cells. Compositions that incorporate these antibodies into chimeric immunotoxin molecules that can be used in medicaments and methods for inhibiting the growth and proliferation of leukemia and lymphoma cells.
摘要翻译：重组免疫毒素是由与细菌或植物毒素融合的抗体的Fv结构域组成的融合蛋白。 RFB4（Fv）-PE38是靶向在B细胞和B细胞恶性肿瘤上表达的CD22的免疫毒素。与RFB4相比，本发明提供了具有改善的结合B细胞和B细胞恶性肿瘤的CD22抗原的能力的抗体和抗体片段。用本发明的抗体和抗体片段制备的免疫毒素对表达CD22的癌细胞具有改善的细胞毒性。将这些抗体并入可用于药物的嵌合免疫毒素分子中的组合物和用于抑制白血病和淋巴瘤细胞生长和增殖的方法。

8. 发明申请

US20110065185A1 MUTATED ANTI-CD22 ANTIBODIES WITH INCREASED AFFINITY TO CD22-EXPRESSING LEUKEMIA CELLS 审中-公开
标题翻译：具有增加CD22表达LEUKEMIA细胞的亲和力的突变型抗CD22抗体
公开(公告)号：US20110065185A1
公开(公告)日：2011-03-17
申请号：US12846625
申请日：2010-07-29
申请人： Ira H. Pastan , Giuliana Salvatore , Richard Beers , Robert J. Kreitman
发明人： Ira H. Pastan , Giuliana Salvatore , Richard Beers , Robert J. Kreitman
IPC分类号： C12N5/10 , C07H21/00 , C12N15/63 , C12N1/21 , C12N1/19
CPC分类号： C07K16/2803 , A61K47/6829 , A61K47/6849 , A61K47/6875 , A61K2039/505 , C07K2317/24 , C07K2317/565 , C07K2317/622 , C07K2317/624
摘要： Recombinant immunotoxins are fusion proteins composed of the Fv domains of antibodies fused to bacterial or plant toxins. RFB4 (Fv)-PE38 is an immunotoxin that targets CD22 expressed on B cells and B cell malignancies. The present invention provides antibodies and antibody fragments that have improved ability to bind the CD22 antigen of B cells and B cell malignancies compared to RFB4. Immunotoxins made with the antibodies and antibody fragments of the invention have improved cytotoxicity to CD22-expressing cancer cells. Compositions that incorporate these antibodies into chimeric immunotoxin molecules that can be used in medicaments and methods for inhibiting the growth and proliferation of leukemia and lymphoma cells.
摘要翻译：重组免疫毒素是由与细菌或植物毒素融合的抗体的Fv结构域组成的融合蛋白。 RFB4（Fv）-PE38是靶向在B细胞和B细胞恶性肿瘤上表达的CD22的免疫毒素。与RFB4相比，本发明提供了具有改善的结合B细胞和B细胞恶性肿瘤的CD22抗原的能力的抗体和抗体片段。用本发明的抗体和抗体片段制备的免疫毒素对表达CD22的癌细胞具有改善的细胞毒性。将这些抗体并入可用于药物的嵌合免疫毒素分子中的组合物和用于抑制白血病和淋巴瘤细胞生长和增殖的方法。

9. 发明授权

US10683362B2 Recombinant immunotoxin targeting mesothelin 有权
公开(公告)号：US10683362B2
公开(公告)日：2020-06-16
申请号：US14115131
申请日：2012-05-04
申请人： Ira H. Pastan , John Weldon , Richard Beers
发明人： Ira H. Pastan , John Weldon , Richard Beers
IPC分类号： C07K16/30 , C07K14/21 , A61K39/00 , A61K47/68
摘要： Mesothelin is a differentiation antigen present on the surface of ovarian cancers, mesotheliomas and several other types of human cancers. Because among normal tissues, mesothelin is only present on mesothelial cells, it represents a good target for antibody mediated delivery of cytotoxic agents. The present invention is directed to improved recombinant immunotoxins comprising anti-mesothelin antibodies, including Fv molecules with particularly high affinity for mesothelin, and a Pseudomonas Exotoxin moiety which has been modified to reduce its immunogenicity and protease sensitivity and providing a better cytotoxicity for cells which express mesothelin. The RITs are well-suited for the treatment of cancers of the ovary, stomach, squamous cells, mesotheliomas and other malignant cells expressing mesothelin.

10. 发明申请

US20090004734A1 Mutated Anti-CD22 Antibodies With Increased Affinity To CD22-Expressing Leukemia Cells 有权
标题翻译：突变的抗CD22抗体与CD22表达白血病细胞的亲和力增加
公开(公告)号：US20090004734A1
公开(公告)日：2009-01-01
申请号：US12030828
申请日：2008-02-13
申请人： Ira H. Pastan , Giuliana Salvatore , Richard Beers , Robert J. Kreitman
发明人： Ira H. Pastan , Giuliana Salvatore , Richard Beers , Robert J. Kreitman
IPC分类号： C12N5/10 , C07H21/04 , C12N15/63
CPC分类号： C07K16/2803 , A61K47/6829 , A61K47/6849 , A61K47/6875 , A61K2039/505 , C07K2317/24 , C07K2317/565 , C07K2317/622 , C07K2317/624
摘要： Recombinant immunotoxins are fusion proteins composed of the Fv domains of antibodies fused to bacterial or plant toxins. RFB4 (Fv)-PE38 is an immunotoxin that targets CD22 expressed on B cells and B cell malignancies. The present invention provides antibodies and antibody fragments that have improved ability to bind the CD22 antigen of B cells and B cell malignancies compared to RFB4. Immunotoxins made with the antibodies and antibody fragments of the invention have improved cytotoxicity to CD22-expressing cancer cells. Compositions that incorporate these antibodies into chimeric immunotoxin molecules that can be used in medicaments and methods for inhibiting the growth and proliferation of leukemia and lymphoma cells.
摘要翻译：重组免疫毒素是由与细菌或植物毒素融合的抗体的Fv结构域组成的融合蛋白。 RFB4（Fv）-PE38是靶向在B细胞和B细胞恶性肿瘤上表达的CD22的免疫毒素。与RFB4相比，本发明提供了具有改善的结合B细胞和B细胞恶性肿瘤的CD22抗原的能力的抗体和抗体片段。用本发明的抗体和抗体片段制备的免疫毒素对表达CD22的癌细胞具有改善的细胞毒性。将这些抗体并入可用于药物的嵌合免疫毒素分子中的组合物和用于抑制白血病和淋巴瘤细胞生长和增殖的方法。

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