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1. 发明授权

US6147203A Recombinant disulfide-stabilized polypeptide fragments having binding specificity 失效
标题翻译：具有结合特异性的重组二硫键稳定的多肽片段
公开(公告)号：US6147203A
公开(公告)日：2000-11-14
申请号：US2753
申请日：1998-01-05
申请人： Ira H. Pastan , Byungkook Lee , Sun-Hee Jung , Ulrich Brinkmann
发明人： Ira H. Pastan , Byungkook Lee , Sun-Hee Jung , Ulrich Brinkmann
IPC分类号： C12N15/02 , A61K38/00 , A61K39/395 , A61K47/48 , A61P35/00 , C07K14/725 , C07K16/00 , C07K17/00 , C12N15/09 , C12P21/08 , C07H21/02 , C07H21/04
CPC分类号： C07K14/7051 , A61K47/48484 , A61K47/48507 , C07K16/00 , A61K38/00 , C07K2319/00 , C07K2319/33 , C07K2319/55 , Y10S530/866 , Y10S530/867
摘要： The present invention relates to disulfide-stabilized recombinant polypeptide molecules which have the binding ability and specificity for another peptide, such as the variable region of an antibody molecule. Methods of producing these molecules and nucleic acid sequences encoding these molecules are also described. In particular, the invention discloses Fv antibody fragments stabilized by a disulfide bond connecting the V.sub.H and V.sub.L regions of the Fv fragment. The .alpha. and .beta. chains of T cell receptors may be similarly stabilized by means described in the invention.
摘要翻译：本发明涉及对另一种肽（例如抗体分子的可变区）具有结合能力和特异性的二硫键稳定的重组多肽分子。还描述了生产这些分子的方法和编码这些分子的核酸序列。特别地，本发明公开了通过连接Fv片段的VH和VL区的二硫键稳定的Fv抗体片段。 T细胞受体的α链和β链可以通过本发明所述的手段相似地稳定。

2. 发明授权

US5747654A Recombinant disulfide-stabilized polypeptide fragments having binding specificity 失效
公开(公告)号：US5747654A
公开(公告)日：1998-05-05
申请号：US77252
申请日：1993-06-14
申请人： Ira H. Pastan , Byungkook Lee , Sun-Hee Jung , Ulrich Brinkmann
发明人： Ira H. Pastan , Byungkook Lee , Sun-Hee Jung , Ulrich Brinkmann
IPC分类号： C12N15/02 , A61K38/00 , A61K39/395 , A61K47/48 , A61P35/00 , C07K14/725 , C07K16/00 , C07K17/00 , C12N15/09 , C12P21/08 , C07K19/00 , C07K16/46
CPC分类号： C07K14/7051 , A61K47/48484 , A61K47/48507 , C07K16/00 , A61K38/00 , C07K2319/00 , C07K2319/33 , C07K2319/55 , Y10S530/866 , Y10S530/867
摘要： The present invention relates to disulfide-stabilized recombinant polypeptide molecules which have the binding ability and specificity for another peptide, such as the variable region of an antibody molecule. Methods of producing these molecules and nucleic acid sequences encoding these molecules are also described. In particular, the invention discloses Fv antibody fragments stabilized by a disulfide bond connecting the V.sub.H and V.sub.L regions of the Fv fragment. The .alpha. and .beta. chains of T cell receptors may be similarly stabilized by means described in the invention.

3. 发明授权

US06558672B1 Methods of making recombinant disulfide-stabilized polypeptide fragments having binding specificity 有权
标题翻译：制备具有结合特异性的重组二硫键稳定的多肽片段的方法
公开(公告)号：US06558672B1
公开(公告)日：2003-05-06
申请号：US09657274
申请日：2000-09-07
申请人： Ira H. Pastan , Byungkook Lee , Sun-Hee Jung , Ulrich Brinkmann
发明人： Ira H. Pastan , Byungkook Lee , Sun-Hee Jung , Ulrich Brinkmann
IPC分类号： A61K3900
CPC分类号： C07K14/7051 , A61K38/00 , A61K47/6829 , A61K47/6835 , C07K16/00 , C07K2319/00 , C07K2319/33 , C07K2319/55 , Y10S530/866 , Y10S530/867
摘要： The present invention relates to disulfide-stabilized recombinant polypeptide molecules which have the binding ability and specificity for another peptide, such as the variable region of an antibody molecule. Methods of producing these molecules and nucleic acid sequences encoding these molecules are also described. In particular, the invention discloses Fv antibody fragments stabilized by a disulfide bond connecting the VH and VL regions of the Fv fragment. The &agr; and &bgr; chains of T cell receptors may be similarly stabilized by means described in the invention.
摘要翻译：本发明涉及对另一种肽（例如抗体分子的可变区）具有结合能力和特异性的二硫键稳定的重组多肽分子。还描述了生产这些分子的方法和编码这些分子的核酸序列。特别地，本发明公开了通过连接Fv片段的VH和VL区的二硫键稳定的Fv抗体片段。 T细胞受体的α链和β链可以通过本发明所述的手段相似地稳定。

4. 发明授权

US07897355B2 Gene expressed in prostate cancer and methods of use 失效
标题翻译：在前列腺癌中表达的基因和使用方法
公开(公告)号：US07897355B2
公开(公告)日：2011-03-01
申请号：US12193604
申请日：2008-08-18
申请人： Ira H. Pastan , Tapan K. Bera , Curt Wolfgang , Byungkook Lee , James Vincent
发明人： Ira H. Pastan , Tapan K. Bera , Curt Wolfgang , Byungkook Lee , James Vincent
IPC分类号： G01N33/53
CPC分类号： C07K14/47 , A01K2217/05 , A61K39/00
摘要： A new polypeptide is disclosed that is specifically detected in the cells of the prostate, termed Novel Gene Expressed in Prostate (NGEP). Polynucleotides encoding NGEP are also disclosed, as are vectors including these polynucleotides. Host cells transformed with these polynucleotides are also disclosed. Antibodies are disclosed that specifically bind NGEP. Methods are disclosed for using an NGEP polypeptide, an antibody that specifically binds NGEP, or a polynucleotide encoding NGEP. Assays are disclosed for the detection prostate cancer. Pharmaceutical compositions including an NGEP polypeptide, an antibody that specifically binds NGEP, or a polynucleotide encoding NGEP are also disclosed. These pharmaceutical compositions are of use in the treatment of prostate cancer.
摘要翻译：公开了在前列腺细胞中被特异性检测到的新的多肽，称为前列腺中表达的新基因（NGEP）。还公开了编码NGEP的多核苷酸，以及包括这些多核苷酸的载体也是公开的。还公开了用这些多核苷酸转化的宿主细胞。公开了特异性结合NGEP的抗体。公开了使用NGEP多肽，特异性结合NGEP的抗体或编码NGEP的多核苷酸的方法。公开了检测前列腺癌的检测。还公开了包括NGEP多肽，特异性结合NGEP的抗体或编码NGEP的多核苷酸的药物组合物。这些药物组合物可用于治疗前列腺癌。

5. 发明申请

US20090142341A1 Mutated pseudomonas exotoxins with reduced antigenicity 有权
标题翻译：具有降低的抗原性的突变的假单胞菌外毒素
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。

6. 发明申请

US20090202552A1 GENE EXPRESSED IN PROSTATE CANCER AND METHODS OF USE 失效
标题翻译：前列腺癌中表达的基因和使用方法
公开(公告)号：US20090202552A1
公开(公告)日：2009-08-13
申请号：US12193604
申请日：2008-08-18
申请人： Ira H. Pastan , Tapan K. Bera , Curt Wolfgang , Byungkook Lee , James Vincent
发明人： Ira H. Pastan , Tapan K. Bera , Curt Wolfgang , Byungkook Lee , James Vincent
IPC分类号： A61K39/395 , C07K14/00 , C07H21/00 , C12N15/63 , C12N5/00 , C07K16/30 , G01N33/53 , G01N33/574 , C12Q1/68 , A61K38/16 , A61K31/7052 , A61P35/00
CPC分类号： C07K14/47 , A01K2217/05 , A61K39/00
摘要： A new polypeptide is disclosed that is specifically detected in the cells of the prostate, termed Novel Gene Expressed in Prostate (NGEP). Polynucleotides encoding NGEP are also disclosed, as are vectors including these polynucleotides. Host cells transformed with these polynucleotides are also disclosed. Antibodies are disclosed that specifically bind NGEP. Methods are disclosed for using an NGEP polypeptide, an antibody that specifically binds NGEP, or a polynucleotide encoding NGEP. Assays are disclosed for the detection prostate cancer. Pharmaceutical compositions including an NGEP polypeptide, an antibody that specifically binds NGEP, or a polynucleotide encoding NGEP are also disclosed. These pharmaceutical compositions are of use in the treatment of prostate cancer.
摘要翻译：公开了在前列腺细胞中被特异性检测到的新的多肽，称为前列腺中表达的新基因（NGEP）。还公开了编码NGEP的多核苷酸，以及包括这些多核苷酸的载体也是公开的。还公开了用这些多核苷酸转化的宿主细胞。公开了特异性结合NGEP的抗体。公开了使用NGEP多肽，特异性结合NGEP的抗体或编码NGEP的多核苷酸的方法。公开了检测前列腺癌的检测。还公开了包括NGEP多肽，特异性结合NGEP的抗体或编码NGEP的多核苷酸的药物组合物。这些药物组合物可用于治疗前列腺癌。

7. 发明授权

US07521054B2 Reduction of the nonspecific animal toxicity of immunotoxins by mutating the framework regions of the Fv to lower the isoelectric point 有权
标题翻译：通过突变Fv的框架区域来降低免疫毒素的非特异性动物毒性以降低等电点
公开(公告)号：US07521054B2
公开(公告)日：2009-04-21
申请号：US10416129
申请日：2001-11-16
申请人： Ira H. Pastan , Masanori Onda , Satoshi Nagata , Yasuo Tsutsumi , James J. Vincent , Robert J. Kreitman , George Vasmatzis , Byungkook Lee
发明人： Ira H. Pastan , Masanori Onda , Satoshi Nagata , Yasuo Tsutsumi , James J. Vincent , Robert J. Kreitman , George Vasmatzis , Byungkook Lee
IPC分类号： A61K47/48 , C07K16/18 , C07K16/28
CPC分类号： C07K16/28 , A61K47/6829 , A61K47/6849 , A61K47/6867 , A61K2039/505 , C07K14/21 , C07K16/00 , C07K16/18 , C07K16/2803 , C07K16/2866 , C07K16/2896 , C07K16/30 , C07K2317/56 , C07K2317/567 , C07K2317/624 , C07K2319/02
摘要： The invention provides recombinant immunotoxins that have been modified from a parental immunotoxin to lower liver toxicity. The immunotoxins are created by specifically mutating charged residues in the framework regions of the heavy chain, the light chain, or both, of the antibody portion or antigen-binding fragment thereof of the parental immunotoxin to reduce the pI of the antibody or fragment. In preferred forms, the antibody portion of the parental is an anti-Tac, anti-mesothelin, or anti-LewisY antigen antibody or antigen-binding fragment, and in particularly preferred forms the antibody portion is an M16 dsFv, a St6 dsFv or a Mt9 dsFv, or a sequence that has at least 90% sequence identity to one of these molecules but retain the particular mutations that lower pI without affecting antibody activity. The invention further provides nucleic acids encoding the recombinant immunotoxins of the invention, expression cassettes comprising the nucleic acids, and host cells comprising the expression cassettes. The invention also provides a method for killing a cell comprising an antigen on the surface of the cell, the method comprising contacting the cell with a recombinant immunotoxin of the invention that has an antibody or antigen-binding fragment thereof that binds specifically to the antigen on the surface of the cell, and uses of immunotoxins of the invention for the manufacture of medicaments.
摘要翻译：本发明提供已经从亲本免疫毒素修饰以降低肝毒性的重组免疫毒素。免疫毒素通过在亲本免疫毒素的抗体部分或其抗原结合片段的重链，轻链或两者的构架区中特异性突变带电残基而产生，以减少抗体或片段的pI。在优选形式中，亲本的抗体部分是抗Tac，抗间皮素或抗LewisY抗原抗体或抗原结合片段，并且在特别优选的形式中，抗体部分是M16 dsFv，St6 dsFv或 Mt9 dsFv或与这些分子之一具有至少90％序列同一性的序列，但保留降低pI而不影响抗体活性的特定突变。本发明还提供编码本发明的重组免疫毒素的核酸，包含核酸的表达盒和包含表达盒的宿主细胞。本发明还提供了一种用于杀死细胞表面上包含抗原的细胞的方法，所述方法包括使细胞与本发明的重组免疫毒素接触，所述重组免疫毒素具有抗体或其抗原结合片段，其特异性与抗原结合细胞的表面，以及本发明的免疫毒素用于制备药物的用途。

8. 发明授权

US08907060B2 Mutated Pseudomonas exotoxins with reduced antigenicity 有权
标题翻译：具有降低的抗原性的突变的假单胞菌外毒素
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。

9. 发明授权

US07816087B2 Gene expressed in prostate cancer and methods of use 失效
标题翻译：在前列腺癌中表达的基因和使用方法
公开(公告)号：US07816087B2
公开(公告)日：2010-10-19
申请号：US10495663
申请日：2002-11-13
申请人： Ira H. Pastan , Tapan K. Bera , Curt Wolfgang , Byungkook Lee , James Vincent
发明人： Ira H. Pastan , Tapan K. Bera , Curt Wolfgang , Byungkook Lee , James Vincent
IPC分类号： G01N33/53
CPC分类号： C07K14/47 , A01K2217/05 , A61K39/00
摘要： A new polypeptide is disclosed that is specifically detected in the cells of the prostate, termed Novel Gene Expressed in Prostate (NGEP). Polynucleotides encoding NGEP are also disclosed, as are vectors including these polynucleotides. Host cells transformed with these polynucleotides are also disclosed. Antibodies are disclosed that specfically bind NGEP. Methods are disclosed for using an NGEP polypeptide, an antibody that specifically binds NGEP, or a polynucleotide encoding NGEP. Assays are disclosed for the detection prostate cancer. Pharamaceutical compositions including an NGEP polypeptide, an antibody that specifically binds NGEP, or a polynucleotide encoding NGEP are also disclosed. These pharmaceutical compositions are of use in the treatment of prostate cancer.
摘要翻译：公开了在前列腺细胞中被特异性检测到的新的多肽，称为前列腺中表达的新基因（NGEP）。还公开了编码NGEP的多核苷酸，以及包括这些多核苷酸的载体也是公开的。还公开了用这些多核苷酸转化的宿主细胞。公开了特异性结合NGEP的抗体。公开了使用NGEP多肽，特异性结合NGEP的抗体或编码NGEP的多核苷酸的方法。公开了检测前列腺癌的检测。还公开了包括NGEP多肽，特异性结合NGEP的抗体或编码NGEP的多核苷酸的药物组合物。这些药物组合物可用于治疗前列腺癌。

10. 发明授权

US06287562B1 Methods of inhibiting the growth of cells bearing LewisY antigens using B1, B3, or B5 targeted immunoconjugates 失效
标题翻译：使用B1，B3或B5靶向免疫缀合物抑制携带LewisY抗原的细胞生长的方法
公开(公告)号：US06287562B1
公开(公告)日：2001-09-11
申请号：US09227693
申请日：1999-01-08
申请人： Ira Pastan , Itai Benhar , Eduardo A. Padlan , Sun-Hee Jung , Byungkook Lee
发明人： Ira Pastan , Itai Benhar , Eduardo A. Padlan , Sun-Hee Jung , Byungkook Lee
IPC分类号： A61K39395
CPC分类号： G01N33/57419 , A61K38/00 , A61K47/6851 , C07K14/21 , C07K16/18 , C07K16/30 , C07K16/34 , C07K19/00 , C07K2317/24 , C07K2317/56 , C07K2317/622 , C07K2319/00 , G01N33/57446 , G01N33/57449 , G01N33/57492
摘要： The invention provides methods for inhibiting the growth of a cell bearing a LewisY antigen. The methods involve contacting the cell with a composition comprising an Fv region of a light chain of a monoclonal antibody selected from B1, B3, and B5, and the Fv region of a humanized heavy chain of a monoclonal antibody independently selected from B1, B3, and B5, provided that if the heavy and the light chains are from the same antibody, the residue at position 95 of the heavy chain is a serine, and, if the antibody chain is from B3, the residue at position 4 of the light chain can be a leucine and the residue at position 82b of the heavy chain can be an arginine. The Fv regions are joined to an effector molecule selected from a chemotherapeutic agent, a toxin, a radioisotope, and a liposome loaded with a chemotherapeutic agent. In preferred embodiments, the heavy chain and the light chain are recombinantly fused, and the Fv regions are recombinantly fused to a toxin.
摘要翻译：本发明提供了抑制携带LewisY抗原的细胞生长的方法。所述方法包括使细胞与包含选自B1，B3和B5的单克隆抗体的轻链的Fv区和单独抗体的人源化重链的Fv区的组合物接触，所述单克隆抗体独立地选自B1，B3，和B5，条件是如果重链和轻链来自相同的抗体，则重链位置95处的残基是丝氨酸，并且如果抗体链来自B3，则轻链第4位的残基可以是亮氨酸，重链位置82b处的残基可以是精氨酸。 Fv区连接到选自化疗剂，毒素，放射性同位素和装载有化学治疗剂的脂质体的效应分子。在优选的实施方案中，将重链和轻链重组融合，并将Fv区重组融合至毒素。

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