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1. 发明授权

US09206240B2 Pseudomonas exotoxin A with less immunogenic B cell epitopes 有权
标题翻译：具有较少免疫原性B细胞表位的假单胞菌外毒素A
公开(公告)号：US09206240B2
公开(公告)日：2015-12-08
申请号：US14241782
申请日：2012-09-13
申请人： Ira H. Pastan , Masanori Onda , Wenhai Liu
发明人： Ira H. Pastan , Masanori Onda , Wenhai Liu
IPC分类号： A61K38/16 , C07K14/21 , A61P35/00 , C07K16/28 , C07K16/12 , A61K47/48 , A61K38/00
CPC分类号： A61K38/164 , A61K38/00 , A61K47/48484 , C07K14/21 , C07K16/1214 , C07K16/2851 , C07K16/2896 , C07K16/30 , C07K2317/34 , C07K2317/56 , C07K2317/622 , C07K2319/01 , C07K2319/55
摘要： The invention provides a Pseudomonas exotoxin A (PE) comprising an amino acid sequence having a substitution of one or more of amino acid residues E420, D463, Y481, L516, R563, D581, D589, and K606, wherein the amino acid residues are defined by reference to SEQ ID NO: 1. 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：本发明提供了一种假单胞菌外毒素A（PE），其包含具有氨基酸残基E420，D463，Y481，L516，R563，D581，D589和K606中的一个或多个取代的氨基酸序列，其中定义了氨基酸残基本发明还提供了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. 发明申请

US20130171178A1 Immunogenic Peptides of Xage-1 审中-公开
标题翻译： Xage-1免疫原性肽
公开(公告)号：US20130171178A1
公开(公告)日：2013-07-04
申请号：US10582703
申请日：2004-12-13
申请人： Jay A. Berzofsky , Ira H. Pastan , Masaki Terabe
发明人： Jay A. Berzofsky , Ira H. Pastan , Masaki Terabe
IPC分类号： C07K7/06 , A61K39/00 , A61K45/06 , C07K7/08 , C12P21/06 , C07H21/04 , C07K14/82
CPC分类号： C07K7/06 , A61K39/0011 , A61K45/06 , C07K14/4748
摘要： XAGE-1 is a gene expressed in a number of important human cancers, including prostate cancer, lung cancer, breast cancer, ovarian cancer, glioblastoma, pancreatic cancer, and melanoma. It has now been discovered that peptides of fifty or fewer amino acids comprising the sequence X1X2X3PSAPSPX4 (SEQ ID NO:5), where X1 is any amino acid and is preferably G or Y; X2 is selected from the group consisting of L, M, A, I, V, and T, with L and M being preferred; X3 is a hydrophobic residue, M or A; and X4 is V, M, L, A, I, or T, and is preferably V, bind to the HLA-A2 MHC class I molecule, and can be used to raise immune responses to XAGE-1-expressing cancers. In some embodiments, the P at position 7, the S at position 8, or the P at position 9, can be omitted to create a 9 amino acid peptide. The invention provides immunogenic peptides, nucleic acids encoding them, vectors comprising the nucleic acids, uses of the peptides and nucleic acids for manufacture of medicaments, methods of using the peptides and nucleic acids, and compositions of the peptides or nucleic acids in pharmaceutically acceptable carriers.
摘要翻译： XAGE-1是在许多重要的人类癌症中表达的基因，包括前列腺癌，肺癌，乳腺癌，卵巢癌，胶质母细胞瘤，胰腺癌和黑素瘤。现在已经发现包含序列X1X2X3PSAPSPX4（SEQ ID NO：5）的五十个或更少的氨基酸的肽，其中X 1是任何氨基酸并且优选是G或Y; X2选自L，M，A，I，V和T，其中L和M是优选的; X3是疏水残基M或A; 并且X4是V，M，L，A，I或T，并且优选为V，结合HLA-A2 MHC I类分子，并且可用于引起对表达XAGE-1的癌症的免疫应答。在一些实施方案中，可以省略位置7处的P，位置8处的S或位置9处的P，以产生9个氨基酸的肽。本发明提供免疫原性肽，编码它们的核酸，包含核酸的载体，肽和核酸用于制备药物的用途，使用肽和核酸的方法，以及肽或核酸在药学上可接受的载体中的组合物。

3. 发明授权

US08039593B2 Antibodies and immunotoxins that target human glycoprotein NMB 有权
标题翻译：针对人类糖蛋白NMB的抗体和免疫毒素
公开(公告)号：US08039593B2
公开(公告)日：2011-10-18
申请号：US12092228
申请日：2006-10-31
申请人： Chien-Tsun Kuan , Darell D Bigner , Ira H Pastan
发明人： Chien-Tsun Kuan , Darell D Bigner , Ira H Pastan
IPC分类号： C07K16/00 , A61K39/395
CPC分类号： C07K16/28 , A61K47/6817 , A61K2039/505 , C07K16/1214 , C07K16/30 , C07K2317/565 , C12N15/00 , G01N33/57484
摘要： The invention provides high affinity antibodies suitable for forming immunotoxins that inhibit the growth of cells expressing human glycoprotein NMB, including glioblastoma multiform cells, anaplastic astrocytoma cells, anaplastic oligodendroglioma cells, oligodendroglioma cells, and melanoma cells.
摘要翻译：本发明提供了适合于形成抑制表达人糖蛋白NMB的细胞生长的免疫毒素的高亲和力抗体，包括成胶质细胞瘤多形细胞，间变性星形细胞瘤细胞，间变性少突神经胶质瘤细胞，少突胶质细胞瘤细胞和黑素瘤细胞。

4. 发明申请

US20110020344A1 HUMAN MONOCLONAL ANTIBODIES SPECIFIC FOR CD22 有权
标题翻译： CD22的人体单克隆抗体特异性
公开(公告)号：US20110020344A1
公开(公告)日：2011-01-27
申请号：US12934214
申请日：2009-04-01
申请人： Dimiter S. Dimitrov , Xiaodong Xiao , Ira H. Pastan
发明人： Dimiter S. Dimitrov , Xiaodong Xiao , Ira H. Pastan
IPC分类号： A61K39/395 , C07K16/28 , C07H21/00 , C12N15/63 , G01N33/574 , C12N5/10 , A61P35/00 , A61P35/02
CPC分类号： C07K16/2803 , A61K38/164 , A61K38/45 , A61K39/00 , A61K39/39558 , A61K47/6829 , A61K47/6849 , A61K47/6867 , A61K2039/505 , C07K16/28 , C07K16/2896 , C07K2317/21 , C07K2317/51 , C07K2317/515 , C07K2317/55 , C07K2317/565 , C07K2317/622 , C07K2317/92 , C12Y204/02036 , G01N33/57492 , G01N2333/70503
摘要： Disclosed herein are isolated human monoclonal antibodies that specifically bind human CD22 with a dissociation constant (Kd) of 25 nM or less. Nucleic acids encoding these antibodies, expression vectors including these nucleic acid molecules, and isolated host cells that express the nucleic acid molecules are also disclosed. The antibodies can be used to detect human CD22 in a sample. In some cases, CD22 is soluble CD22. Methods of diagnosing a B-cell malignancy, or confirming a B-cell malignancy diagnosis, are disclosed herein that utilize these antibodies. Methods of treating a subject with a B-cell malignancy are also disclosed.
摘要翻译：本文公开了分离的人单克隆抗体，其具有25nM或更低的解离常数（Kd）特异性结合人CD22。还公开了编码这些抗体的核酸，包括这些核酸分子的表达载体和表达核酸分子的分离的宿主细胞。抗体可用于检测样品中的人CD22。在某些情况下，CD22是可溶性CD22。本文公开了利用这些抗体的诊断B细胞恶性肿瘤或确认B细胞恶性肿瘤诊断的方法。还公开了治疗患有B细胞恶性肿瘤的受试者的方法。

5. 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。

6. 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。

7. 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.

8. 发明授权

US5635599A Fusion proteins comprising circularly permuted ligands 失效
标题翻译：包含环状配位体的融合蛋白
公开(公告)号：US5635599A
公开(公告)日：1997-06-03
申请号：US225224
申请日：1994-04-08
申请人： Ira H. Pastan , Robert J. Kreitman , Raj K. Puri
发明人： Ira H. Pastan , Robert J. Kreitman , Raj K. Puri
IPC分类号： A61K38/00 , A61K47/48 , C07K1/107 , C07K14/535 , C07K14/54 , C07K14/55 , C07K16/30 , C12N15/62 , C07K19/00
CPC分类号： C07K16/30 , A61K47/48238 , A61K47/48269 , C07K1/107 , C07K14/535 , C07K14/5406 , C07K14/55 , C12N15/62 , A61K38/00 , C07K2317/77 , C07K2319/00 , C07K2319/09 , C07K2319/55 , C07K2319/75 , C07K2319/80
摘要： The present invention provides for circularly permuted ligands which possess specificity and binding affinity comparable to or greater than the specificity and binding affinity of the original (unpermuted) ligand. The invention further provides for novel fusion proteins comprising a circularly permuted ligand fused to one or more proteins of interest.
摘要翻译：本发明提供了具有与原始（未被忽略的）配体的特异性和结合亲和力相当或更大的特异性和结合亲和力的环状置换的配体。本发明还提供了包含与一种或多种感兴趣的蛋白质融合的环状置换配体的新型融合蛋白。

9. 发明授权

US5206352A Compositions for clones containing DNA sequences associated with multidrug resistance in human cells 失效
标题翻译：含有与人类细胞中多药耐药相关的DNA序列的克隆的组合物
公开(公告)号：US5206352A
公开(公告)日：1993-04-27
申请号：US622836
申请日：1990-09-24
申请人： Igor B. Roninson , Ira H. Pastan , Michael M. Gottesman
发明人： Igor B. Roninson , Ira H. Pastan , Michael M. Gottesman
IPC分类号： A61K38/00 , A61K47/48 , C07K14/705 , C12Q1/68
CPC分类号： C12Q1/6876 , A61K47/48384 , C07K14/705 , A61K38/00 , C12Q2600/106 , C12Q2600/158
摘要： Genomic and cDNA clones of human genes which are selectively amplified or overexpressed in multidrug-resistant human tumor cells were isolated. Such clones may be used as probes in diagnostic tests to detect chemotherapy-resistant tumor cells and to predict tumor response to chemotherapy. The complete nucleotide sequence of the coding region of the human mdr1 gene and the complete corresponding amino acid sequence are disclosed.
摘要翻译：分离了在多重耐药性人肿瘤细胞中选择性扩增或过表达的人基因的基因组和cDNA克隆。这样的克隆可以用作诊断测试中的探针，以检测耐化学药物的肿瘤细胞并预测肿瘤对化学疗法的反应。公开了人mdr1基因的编码区的完整核苷酸序列和完全相应的氨基酸序列。

10. 发明授权

US4958009A 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：US4958009A
公开(公告)日：1990-09-18
申请号：US69867
申请日：1987-07-06
申请人： Michael J. Bjorn , David J. FitzGerald , Arthur E. Frankel , Walter J. Laird , Ira H. Pastan , David B. Ring , Mark C. Willingham , Jeffrey L. Windelhake
发明人： Michael J. Bjorn , David J. FitzGerald , Arthur E. Frankel , Walter J. Laird , Ira H. Pastan , David B. Ring , Mark C. Willingham , Jeffrey L. Windelhake
IPC分类号： C12N15/02 , A61K38/00 , A61K39/395 , A61K47/00 , A61K47/48 , A61P35/00 , C07K14/00 , C07K14/195 , C07K14/37 , C07K14/41 , C07K14/415 , C07K16/00 , C07K16/30 , C07K19/00 , C12N5/00 , C12N5/10 , C12P21/00 , C12P21/08 , C12R1/91 , G01N33/574 , G01N33/577
CPC分类号： C07K16/30 , A61K47/48638 , A61K38/00 , Y10S424/804 , Y10S424/807 , Y10S514/885 , Y10S530/808 , Y10S530/864
摘要： Immunotoxins comprising a cytotoxic moiety and monoclonal antibodies which bind to human ovarian cancer tissue having at least one of the following capabilities are claimed: cytotoxic ID.sub.50 of 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 to which the monoclonal antibody of the immunotoxin bind are identified and characterize the immunotoxins. Methods of killing human ovarian cancer cells, retarding the growth of human ovarian cancer tumors in mammals or extending the survival of mammals carrying human ovarian cancer tumors are claimed.
摘要翻译：包含细胞毒素部分的免疫毒素和结合至少具有以下能力之一的人卵巢癌组织的单克隆抗体是要求保护的：针对人卵巢癌细胞的10nM或更小的细胞毒性ID50，哺乳动物或延伸中人卵巢癌肿瘤生长的延迟携带人卵巢癌肿瘤的哺乳动物的存活。识别免疫毒素结合的单克隆抗体的抗原并表征免疫毒素。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或延长携带人卵巢癌肿瘤的哺乳动物的存活。

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