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1.发明申请Elisa assay of serum soluble cd22 to assess tumor burnden/relapse in subjects with leukemia and lymphoma 审中-公开Elisa测定血清可溶性cd22以评估白血病和淋巴瘤受试者的肿瘤烧伤/复发公开(公告)号：US20050244828A1
公开(公告)日：2005-11-03
申请号：US10514910
申请日：2003-05-20
IPC分类号： A61B20060101 , A61K39/395 , C07K16/00 , C07K16/28 , C12Q1/68 , G01N33/50 , G01N33/53 , G01N33/574
CPC分类号： C07K16/2803 , A61K2039/505 , G01N33/5052 , G01N33/57426 , G01N2333/70596
摘要： Disclosed herein are methods of using previously unknown soluble forms of CD22 (sCD22) present in the serum of subjects with B-cell leukemias and lymphomas to assess tumor burden in the subjects. Also disclosed are methods of diagnosing or prognosing development or progression of a B-cell lymphoma or leukemia in a subject, including detecting sCD22 in a body fluid sample taken or derived from the subject, for instance serum.
摘要翻译： 本文公开了使用存在于患有B细胞白血病和淋巴瘤的受试者血清中的先前未知的可溶形式的CD22（sCD22）的方法来评估受试者的肿瘤负担。 还公开了诊断或预测受试者中B细胞淋巴瘤或白血病的发展或进展的方法，包括检测取自或衍生自受试者的体液样品中的sCD22，例如血清。
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2.发明授权Recombinant antibodies and immunoconjugates targeted to CD-22 bearing cells and tumors 有权靶向CD-22携带细胞和肿瘤的重组抗体和免疫缀合物公开(公告)号：US09592304B2
公开(公告)日：2017-03-14
申请号：US12433737
申请日：2009-04-30
IPC分类号： A61K39/395 , A61K47/48 , C07K16/28 , A61K38/00
CPC分类号： A61K47/48561 , A61K38/00 , A61K47/6849 , C07K16/2803 , C07K2319/00
摘要： Methods and compositions relating to anti-CD22 antibodies with high binding affinity, and immunoconjugates comprising the anti-CD22 antibody linked to a therapeutic agent such as a Pseudomonas exotoxin or a detectable label. The invention provides diagnostic methods, and means to inhibit the growth of malignant B cells.
摘要翻译： 与具有高结合亲和力的抗CD22抗体相关的方法和组合物，以及包含与治疗剂如假单胞菌外毒素或可检测标记物连接的抗-CD22抗体的免疫偶联物。 本发明提供诊断方法和抑制恶性B细胞生长的手段。
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3.发明申请公开(公告)号：US20060193771A1
公开(公告)日：2006-08-31
申请号：US10516766
申请日：2003-06-11
申请人： Ira Pastan , Satoshi Nagata , Masanori Onda , Yoshito Numata , Kenneth Santora , Richard Beers , Robert Kreitman , Abhishek Sinha
发明人： Ira Pastan , Satoshi Nagata , Masanori Onda , Yoshito Numata , Kenneth Santora , Richard Beers , Robert Kreitman , Abhishek Sinha
IPC分类号： A61K39/395 , A61K51/00 , C07K16/46 , C07K16/30
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。
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4.发明申请Mutated anti-cd22 antibodies with increased affinity to cd22-expressing leukemia cells 有权突变的抗cd22抗体与对表达CD22的白血病细胞的亲和性增加公开(公告)号：US20050118182A1
公开(公告)日：2005-06-02
申请号：US10490535
申请日：2002-09-25
申请人： Ira Pastan , Giuliana Salvatore , Richard Beers , Robert Kreitman
发明人： Ira Pastan , Giuliana Salvatore , Richard Beers , Robert Kreitman
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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5.发明授权Mutated anti-CD22 antibodies with increased affinity to CD22-expressing leukemia cells 有权突变的抗CD22抗体对表达CD22的白血病细胞的亲和力增加公开(公告)号：US08809502B2
公开(公告)日：2014-08-19
申请号：US13438725
申请日：2012-04-03
申请人： Ira Pastan , Giuliana Salvatore , Richard Beers , Robert Kreitman
发明人： Ira Pastan , Giuliana Salvatore , Richard Beers , Robert Kreitman
IPC分类号： A61K39/00
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。
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6.发明申请RECOMBINANT ANTIBODIES AND IMMUNOCONJUGATES TARGETED TO CD-22 BEARING CELLS AND TUMORS 审中-公开靶向CD-22轴承细胞和肿瘤的重组抗体和免疫球蛋白公开(公告)号：US20090305411A1
公开(公告)日：2009-12-10
申请号：US12433737
申请日：2009-04-30
CPC分类号： A61K47/48561 , A61K38/00 , A61K47/6849 , C07K16/2803 , C07K2319/00
摘要： Methods and compositions relating to anti-CD22 antibodies with high binding affinity, and immunoconjugates comprising the anti-CD22 antibody linked to a therapeutic agent such as a Pseudomonas exotoxin or a detectable label. The invention provides diagnostic methods, and means to inhibit the growth of malignant B cells.
摘要翻译： 与具有高结合亲和力的抗CD22抗体相关的方法和组合物，以及包含与治疗剂如假单胞菌外毒素或可检测标记物连接的抗-CD22抗体的免疫偶联物。 本发明提供诊断方法和抑制恶性B细胞生长的手段。
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7.发明授权Recombinant antibodies and immunoconjugates targeted to CD-22 bearing cells and tumors 失效靶向CD-22携带细胞和肿瘤的重组抗体和免疫缀合物公开(公告)号：US07541034B1
公开(公告)日：2009-06-02
申请号：US09381497
申请日：1998-03-19
IPC分类号： A61K39/00
CPC分类号： A61K47/48561 , A61K38/00 , A61K47/6849 , C07K16/2803 , C07K2319/00
摘要： Methods and compositions relating to recombinant anti-CD22 antibodies with high binding affinity, and immunoconjugates comprising the anti-CD22 antibody linked to a therapeutic agent such as a Pseudomonas exotoxin or a detectable label. The invention provides diagnostic methods, and means to inhibit the growth of malignant B cells.
摘要翻译： 与具有高结合亲和力的重组抗CD22抗体相关的方法和组合物，以及包含与治疗剂如假单胞菌外毒素或可检测标记物连接的抗CD22抗体的免疫偶联物。 本发明提供诊断方法和抑制恶性B细胞生长的手段。
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公开(公告)号：US20090142341A1
公开(公告)日：2009-06-04
申请号：US11997202
申请日：2006-07-25
申请人： Ira H. Pastan , Masanori Onda , Satoshi Nagata , David Fitzgerald , Robert Kreitman , Byungkook Lee
发明人： Ira H. Pastan , Masanori Onda , Satoshi Nagata , David Fitzgerald , Robert Kreitman , Byungkook Lee
IPC分类号： A61K39/395 , C07K14/195 , C07K16/18 , A61K38/16 , C12N15/11
CPC分类号： A61K47/48484 , A61K38/00 , A61K47/6829 , C07K14/21 , C07K2319/33
摘要： The invention provides mutated Pseudomonas exotoxins (PE) that have reduced immunogenicity compared to PEs containing the native sequence. The PEs of the invention have one or more individual mutations of positions of the native sequence of PE that reduce antibody binding to one or more PE epitopes. Nucleic acids encoding the mutated PEs, chimeric molecules comprising them, compositions comprising the chimeric molecules and methods of using them, are also provided.
摘要翻译： 本发明提供与含有天然序列的PE相比具有降低的免疫原性的突变的假单胞菌外毒素（PE）。 本发明的PE具有减少抗体结合至一个或多个PE表位的PE的天然序列的位置的一个或多个个体突变。 还提供了编码突变的PE的核酸，包含其的嵌合分子，包含嵌合分子的组合物及其使用方法。
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9.发明授权公开(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。
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公开(公告)号：US08907060B2
公开(公告)日：2014-12-09
申请号：US11997202
申请日：2006-07-25
申请人： Ira H. Pastan , Masanori Onda , Satoshi Nagata , David Fitzgerald , Robert Kreitman , Byungkook Lee
发明人： Ira H. Pastan , Masanori Onda , Satoshi Nagata , David Fitzgerald , Robert Kreitman , Byungkook Lee
IPC分类号： A61K38/00 , A61K39/395 , C07K14/21 , A61K47/48
CPC分类号： A61K47/48484 , A61K38/00 , A61K47/6829 , C07K14/21 , C07K2319/33
摘要： The invention provides mutated Pseudomonas exotoxins (PE) that have reduced immunogenicity compared to PEs containing the native sequence. The PEs of the invention have one or more individual mutations of positions of the native sequence of PE that reduce antibody binding to one or more PE epitopes. Nucleic acids encoding the mutated PEs, chimeric molecules comprising them, compositions comprising the chimeric molecules and methods of using them, are also provided.
摘要翻译： 本发明提供与含有天然序列的PE相比具有降低的免疫原性的突变的假单胞菌外毒素（PE）。 本发明的PE具有减少抗体结合至一个或多个PE表位的PE的天然序列的位置的一个或多个个体突变。 还提供了编码突变的PE的核酸，包含其的嵌合分子，包含嵌合分子的组合物及其使用方法。
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