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51. 发明授权

US07709252B2 Antibodies, including FV molecules, and immunoconjugates having high binding affinity for mesothelin and methods for their use 有权
标题翻译：包括FV分子的抗体和对间皮素具有高结合亲和力的免疫缀合物及其使用方法
公开(公告)号：US07709252B2
公开(公告)日：2010-05-04
申请号：US12055145
申请日：2008-03-25
申请人： Ira H. Pastan , Partha S. Chowdhury
发明人： Ira H. Pastan , Partha S. Chowdhury
IPC分类号： C12N15/00
CPC分类号： G01N33/57492 , A61K47/6829 , A61K47/6851 , A61K2039/505 , C07K16/3069 , C07K2317/565 , G01N33/57449
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 anti-mesothelin antibodies, including Fv molecules with particularly high affinity for mesothelin, and immunoconjugates employing them. Also described are diagnostic and therapeutic methods using the antibodies. The anti-mesothelin antibodies are well-suited for the diagnosis and 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。本发明涉及抗间皮素抗体，包括对间皮素具有特别高亲和力的Fv分子和使用它们的免疫缀合物。还描述了使用抗体的诊断和治疗方法。抗间皮素抗体非常适合于诊断和治疗卵巢癌，胃癌，鳞状细胞癌，间皮瘤等表达间皮素的恶性细胞癌。

52. 发明申请

US20100047164A1 Anti-Tumor Antibodies 审中-公开
标题翻译：抗肿瘤抗体
公开(公告)号：US20100047164A1
公开(公告)日：2010-02-25
申请号：US12418956
申请日：2009-04-06
申请人： Darell Bigner , Chien-Tsun Kuan , Ira H. Pastan , Ralph Reisfeld
发明人： Darell Bigner , Chien-Tsun Kuan , Ira H. Pastan , Ralph Reisfeld
IPC分类号： A61K51/00 , A61K39/395 , G01N33/574 , C07K16/00
CPC分类号： A61K51/1027 , A61K2039/505 , C07K16/3092 , C07K2317/54 , C07K2317/622 , C07K2319/00 , G01N2800/52
摘要： Chondroition sulfate proteoglycans represent excellent targets for anti-tumor immunotherapy. Antibodies which target such proteoglycans can be used alone, in combinations, armed with a cytotoxic payload or unarmed. Combinations of such antibodies can target different epitopes of the proteoglycans. Internalization of the antibodies can increase the toxicity of the payloads. Single chain variable regions are especially advantageous for such anti-tumor immunotherapy.
摘要翻译：硫酸软骨素蛋白聚糖代表抗肿瘤免疫治疗的良好靶标。靶向这种蛋白聚糖的抗体可以单独使用，组合使用，具有细胞毒性有效载荷或非武装。这些抗体的组合可以靶向蛋白聚糖的不同表位。抗体的内在化可以增加有效载荷的毒性。单链可变区对于这种抗肿瘤免疫治疗特别有利。

53. 发明申请

US20090269343A1 Dual Specific Immunotoxin for Brain Tumor Therapy 审中-公开
标题翻译：双重特异性免疫毒素用于脑肿瘤治疗
公开(公告)号：US20090269343A1
公开(公告)日：2009-10-29
申请号：US12418975
申请日：2009-04-06
申请人： Darell Bigner , Chien-Tsun Kuan , Ira H. Pastan , Charles N. Pegram
发明人： Darell Bigner , Chien-Tsun Kuan , Ira H. Pastan , Charles N. Pegram
IPC分类号： A61K39/395 , C07K16/00 , G01N33/53 , A61P35/00
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。

54. 发明申请

US20090035266A1 IMMUNOGENIC PEPTIDES AND METHODS OF USE 有权
标题翻译：免疫原性和使用方法
公开(公告)号：US20090035266A1
公开(公告)日：2009-02-05
申请号：US12280534
申请日：2007-02-21
申请人： Jeffrey Schlom , Kwong-Yok Tsang , Ira H. Pastan
发明人： Jeffrey Schlom , Kwong-Yok Tsang , Ira H. Pastan
IPC分类号： A61K45/00 , C07K7/00 , C12N15/11 , C12N15/00 , C12N7/00 , A61K35/76 , C12N5/06 , A61P31/00 , G01N33/574 , A61K38/21 , A61K35/12 , A61K38/00 , A61K31/7088 , A61K39/00
CPC分类号： C07K14/4748 , A61K38/08 , A61K39/0011 , C07K14/82 , C12N2799/023 , C12N2800/00 , G01N2333/70517
摘要： The PAGE4 gene is expressed in reproductive tissues, and is expressed in reproductive cancers, such as prostate cancer, uterine cancer, and testicular cancer. Immunogenic PAGE4 polypeptides are disclosed herein, as are nucleic acids encoding the immunogenic PAGE4 polypeptides, vectors including these polynucleotides, and host cells transformed with these vectors. These polypeptides, polynucleotides, vectors, and host cells can be used to induce an immune response to PAGE4. Diagnostic methods to detect PAGE4 are also described.
摘要翻译： PAGE4基因在生殖组织中表达，并在生殖癌中表达，如前列腺癌，子宫癌和睾丸癌。本文公开了免疫原性PAGE4多肽，以及编码免疫原性PAGE4多肽的核酸，包括这些多核苷酸的载体和用这些载体转化的宿主细胞。这些多肽，多核苷酸，载体和宿主细胞可用于诱导对PAGE4的免疫应答。还描述了检测PAGE4的诊断方法。

55. 发明授权

US5863745A Recombinant antibody-toxin fusion protein 失效
标题翻译：重组抗体 - 毒素融合蛋白
公开(公告)号：US5863745A
公开(公告)日：1999-01-26
申请号：US461825
申请日：1995-06-05
申请人： David J. Fitzgerald , Vijay Kumar Chaudhary , Ira H. Pastan , Thomas Alexander Waldmann , Cary L. Queen
发明人： David J. Fitzgerald , Vijay Kumar Chaudhary , Ira H. Pastan , Thomas Alexander Waldmann , Cary L. Queen
IPC分类号： A61K38/00 , A61K39/00 , A61K47/48 , C07K14/21 , C07K14/495 , C07K14/55 , C07K16/28 , C12N15/62 , G01N33/563 , C07K16/46
CPC分类号： A61K47/48561 , A61K47/48369 , A61K47/48484 , C07K14/21 , C07K14/495 , C07K14/55 , C07K16/2866 , C07K16/2896 , C12N15/62 , A61K38/00 , A61K39/00 , C07K2319/00 , C07K2319/55
摘要： The present invention describes recombinant antibody toxin fusion proteins which selectively kill cells bearing appropriate antigens or receptors.
摘要翻译：本发明描述了选择性地杀死携带合适抗原或受体的细胞的重组抗体毒素融合蛋白。

56. 发明授权

US5821238A Recombinant pseudomonas exotoxin with increased activity 失效
标题翻译：具有增加活性的重组假单胞菌外毒素
公开(公告)号：US5821238A
公开(公告)日：1998-10-13
申请号：US461234
申请日：1995-06-05
申请人： Ira H. Pastan , David J. Fitzgerald
发明人： Ira H. Pastan , David J. Fitzgerald
IPC分类号： C12N15/09 , A61K38/00 , A61K38/22 , A61K39/395 , A61P35/00 , C07K14/21 , C07K14/495 , C07K16/28 , C07K16/30 , C07K19/00 , C12N1/21 , C12N15/31 , C12P21/02 , C12R1/19 , C12R1/38 , A61K39/104 , A61K38/43
CPC分类号： C07K16/30 , C07K14/21 , C07K14/495 , C07K16/2881 , A61K38/00 , C07K2319/00 , C07K2319/02 , C07K2319/55 , C07K2319/75 , Y10S424/832 , Y10S530/825
摘要： This invention relates to the production and use of recombinant Pseudomonas-derived toxins modified to increase their toxicity and potency in therapy. More particularly, the invention relates to certain deletions in domain II of the amino acid sequence of Pseudomonas exotoxin the domain which relates to the toxin's natural proteolytic processing.
摘要翻译：本发明涉及重组的假单胞菌衍生的毒素的生产和使用，其被修饰以增加其在治疗中的毒性和效力。更具体地说，本发明涉及涉及毒素天然蛋白水解加工的结构域中假单胞菌外毒素氨基酸序列的结构域II中的某些缺失。

57. 发明授权

US5489525A Monoclonal antibodies to prostate cells 失效
标题翻译：前列腺细胞单克隆抗体
公开(公告)号：US5489525A
公开(公告)日：1996-02-06
申请号：US958140
申请日：1992-10-08
申请人： Ira H. Pastan
发明人： Ira H. Pastan
IPC分类号： A61K38/00 , A61K47/48 , C07K16/28 , C07K16/30 , C12N5/20 , C12P21/08 , G01N33/53 , G01N33/574
CPC分类号： C07K16/28 , A61K47/48561 , A61K47/48607 , C07K16/3038 , A61K38/00 , C07K2319/33 , C07K2319/55 , Y10S436/813
摘要： Monoclonal antibodies are provided which bind to an antigen associated with prostate cells, including prostate cancers. The monoclonal antibodies and recombinant forms thereof are used individually or conjugated radioisotopes to target the compounds to cancerous prostate cells, and thus are useful in a variety of diagnostic procedures.
摘要翻译：提供了与前列腺细胞（包括前列腺癌）相关的抗原结合的单克隆抗体。单克隆抗体及其重组形式单独使用或共轭放射性同位素将化合物靶向癌性前列腺细胞，因此可用于各种诊断程序。

58. 发明授权

US5328984A Recombinant chimeric proteins deliverable across cellular membranes into cytosol of target cells 失效
标题翻译：通过细胞膜递送的重组嵌合蛋白质转移到靶细胞的细胞溶质中
公开(公告)号：US5328984A
公开(公告)日：1994-07-12
申请号：US663455
申请日：1991-03-04
申请人： Ira H. Pastan , Prior Trevor , David J. Fitzgerald , Waldemar Debinski , Clay Siegall
发明人： Ira H. Pastan , Prior Trevor , David J. Fitzgerald , Waldemar Debinski , Clay Siegall
IPC分类号： C07K14/21 , C07K14/495 , C12N9/54 , C07K13/00 , A61K37/02 , C07K15/04
CPC分类号： C07K14/21 , C07K14/495 , C12N9/54 , C07K2319/00 , C07K2319/02
摘要： Proteins that are impermeable and foreign to the eukaryotic cells can now be delivered across cellular membranes into the cytosol of target cells by making a chimeric protein having specific attributes. A method of making such chimeric proteins is disclosed. As an example, a chimeric protein PE-Bar with dual enzymatic activity has been made. The chimeric proteins can be used for cytotoxic, diagnostic or therapeutic purposes, such as for compensating the deficiency or defect of an enzyme or a protein which may be causative of a disease or an abnormality.
摘要翻译：通过制备具有特定属性的嵌合蛋白，现在可以将真核细胞不渗透和外源的蛋白质通过细胞膜递送到靶细胞的胞质溶胶中。公开了制备这种嵌合蛋白质的方法。作为实例，已经制备了具有双重酶活性的嵌合蛋白质PE-Bar。嵌合蛋白质可以用于细胞毒性，诊断或治疗目的，例如用于补偿可能导致疾病或异常的酶或蛋白质的缺乏或缺陷。

59. 发明授权

US4396628A Antiviral activities of dansylcadaverine and closely related compounds 失效
标题翻译：丹参酰胺和密切相关化合物的抗病毒活性
公开(公告)号：US4396628A
公开(公告)日：1983-08-02
申请号：US352599
申请日：1982-02-26
申请人： Ira H. Pastan , Mark C. Willingham
发明人： Ira H. Pastan , Mark C. Willingham
IPC分类号： A61K31/18
CPC分类号： A61K31/18
摘要： The entry of animal viruses into their host cells proceeds via a specialized internalization pathway involving clathrin coated regions of the plasma membrane. In the present invention, there has been examined the effect of dansylcadaverine compared with amantadine and other antiviral agents as to the entry of vesicular stomatitis virus (VSV) into mouse cells. It was found that both compounds inhibit VSV entry. Both compounds inhibit the uptake of .alpha..sub.2 macroglobulin (.alpha.2M), a protein that binds to specific membrane receptors and follows the same route of internalization. Dansylcadaverine is 20 fold more potent than amantadine to the blocking virus and also to the .alpha..sub.2 macroglobulin uptake.
摘要翻译：动物病毒进入其宿主细胞通过涉及质膜的网格蛋白包被的区域的专门的内化途径进行。在本发明中，已经研究了丹参酰胺素与金刚烷胺和其他抗病毒剂相比，对水泡性口炎病毒（VSV）进入小鼠细胞的效果。发现两种化合物都抑制VSV进入。两种化合物均抑制α2巨球蛋白（α2M）的摄取，α2是一种与特异性膜受体结合并遵循相同的内化途径的蛋白质。丹参酰胺素比金刚烷胺对阻断病毒的效力高20倍，而且对于α2巨球蛋白摄取更有效。

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