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61. 发明申请

US20120190826A1 NOVEL ANTIBIOTIC COMPRISING AN ANTIBODY MIMETIC, ITS PREPARATION METHODS AND USES THEREOF 有权
标题翻译：包含抗体的新型抗生素，其制备方法及其用途
公开(公告)号：US20120190826A1
公开(公告)日：2012-07-26
申请号：US13013693
申请日：2011-01-25
申请人： Xiaoqing Qiu
发明人： Xiaoqing Qiu
IPC分类号： C07K16/12 , C12N15/63 , C12P21/00 , C07H21/00
CPC分类号： C07K14/245 , A61K38/00 , A61K47/48484 , A61K47/48507 , A61K47/6829 , A61K47/6835 , A61K2039/505 , C07K16/1217 , C07K2317/565 , C07K2317/567 , C07K2317/569 , C07K2317/60 , C07K2319/01 , C07K2319/30
摘要： The present invention belongs to field of biology and medicine, and especially relates to a novel antibiotic comprising an antibody mimetic antibody, its preparation methods and uses thereof. A novel antibiotic comprising a antibody mimetic covalently bonded to the carboxyl end of a colicin polypeptide or a channel-forming domain polypeptide of a colicin, wherein said colicin is selected from the group consisting of Colicin E1, Ia, Ib, A, B, N; wherein said antibody mimetic being yielded by fusing two complementarity determining regions (CDRs), VHCDR1 and VLCDR3 through a cognate framework region (VHFR2) of an immunoglobulin; wherein said the immunoglobulin specifically recognizes the bacterial porins. Its antibacterial ability is a thousandfold powerful than normal antibiotics. Due to its unique action mechanism, drug resistance resulted in mutation can hardly be acquired by pathogenic bacteria. And the antibiotic will not hurt normal human cells when it kills pathogenic bacteria. Therefore, it can be used for manufacturing antibacterial medicament of killing Neisseria meningitidis, vancomycin-resistant Enterococcus faecalis, methicillin-resistant Staphylococcus aureus, multidrug-resistance Pseudomonas aeruginosa or Mycobacterium tuberculosis.
摘要翻译：本发明属于生物学和医学领域，特别涉及包含抗体模拟抗体的新型抗生素，其制备方法和用途。一种新型抗生素，其包含共价键合到大肠杆菌素多肽的羧基末端的抗体模拟物或者大肠菌素的通道形成结构域多肽，其中所述大肠菌素选自Colicin E1，Ia，Ib，A，B，N ; 其中通过将两个互补决定区（CDR），VHCDR1和VLCDR3通过免疫球蛋白的同源框架区（VHFR2）融合产生所述抗体模拟物; 其中所述免疫球蛋白特异性识别细菌孔蛋白。其抗菌能力比正常抗生素强1000倍。由于其独特的作用机制，导致突变的耐药性几乎不能被致病菌获得。抗生素在杀死病原菌时不会伤害正常的人类细胞。因此，可用于制造杀伤脑膜炎奈瑟菌，万古霉素耐药性粪肠球菌，耐甲氧西林金黄色葡萄球菌，多药耐药铜绿假单胞菌或结核分枝杆菌的抗菌药物。

62. 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。

63. 发明授权

US5980896A Antibodies reactive with human carcinomas 失效
标题翻译：抗体与人类癌反应
公开(公告)号：US5980896A
公开(公告)日：1999-11-09
申请号：US77253
申请日：1993-06-14
申请人： Ingegerd Hellstrom , Karl Erik Hellstrom , Kim Folger Bruce , George J. Schreiber , Clay Siegall , Stephen McAndrew
发明人： Ingegerd Hellstrom , Karl Erik Hellstrom , Kim Folger Bruce , George J. Schreiber , Clay Siegall , Stephen McAndrew
IPC分类号： A61K38/00 , A61K47/48 , A61K51/10 , A61P35/00 , C07K14/415 , C07K16/30 , C12N15/10 , G01N33/574 , A61K39/395 , C07K19/00 , C12N5/12
CPC分类号： A61K47/48569 , A61K47/48407 , A61K47/48415 , A61K47/48484 , A61K51/1045 , A61K51/1087 , C07K14/415 , C07K16/30 , C12N15/10 , G01N33/57484 , A61K2123/00 , A61K38/00 , C07K2317/24 , C07K2317/54 , C07K2317/55 , C07K2317/56 , C07K2317/622 , C07K2317/732 , C07K2317/734 , C07K2317/77 , C07K2319/00
摘要： The present invention relates to novel antibodies, antibody fragments and antibody conjugates and single-chain immunotoxins reactive with human carcinoma cells. More particularly, the antibodies, conjugates and single-chain immunotoxins of the invention include: a murine monoclonal antibody, BR96; a human/murine chimeric antibody, ChiBR96; a F(ab').sub.2 fragment of BR96; ChiBR96-PE, ChiBR96-LysPE40, ChiBR96 F(ab').sub.2 -LysPE40 and ChiBR96 Fab'-LysPE40 conjugates and recombinant BR96 sFv-PE40 immunotoxin. These molecules are reactive with a cell membrane antigen on the surface of human carcinomas. The BR96 antibody and its functional equivalents, displays a high degree of selectivity for carcinoma cells and possess the ability to mediate antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity activity. In addition, the antibodies of the invention internalize within the carcinoma cells to which they bind and are therefore particularly useful for therapeutic applications, for example, as the antibody component of antibody-drug or antibody-toxin conjugates. The antibodies also have a unique feature in that they are cytotoxic when used in the unmodified form, at specified concentrations.
摘要翻译：本发明涉及与人癌细胞反应的新型抗体，抗体片段和抗体缀合物和单链免疫毒素。更具体地，本发明的抗体，缀合物和单链免疫毒素包括：鼠单克隆抗体BR96; 人/鼠嵌合抗体，ChiBR96; BR96的F（ab'）2片段; ChiBR96-PE，ChiBR96-LysPE40，ChiBR96F（ab'）2-LysPE40和ChiBR96 Fab'-LysPE40缀合物和重组BR96sFv-PE40免疫毒素。这些分子与人类癌症表面的细胞膜抗原反应。 BR96抗体及其功能等同物对癌细胞显示出高度的选择性，并具有介导抗体依赖性细胞毒性和补体依赖性细胞毒活性的能力。此外，本发明的抗体内在于它们结合的癌细胞内，因此特别可用于治疗应用，例如作为抗体药物或抗体 - 毒素缀合物的抗体组分。抗体还具有独特的特征，因为当以指定浓度以未修饰的形式使用时，它们是细胞毒性的。

64. 发明授权

US5932214A Treatment for inflammatory bowel disease with VLA-4 blockers 失效
标题翻译：用VLA-4阻滞剂治疗炎症性肠病
公开(公告)号：US5932214A
公开(公告)日：1999-08-03
申请号：US950660
申请日：1997-10-15
申请人： Roy R. Lobb , Linda C. Burkly
发明人： Roy R. Lobb , Linda C. Burkly
IPC分类号： A61K38/00 , A61K38/17 , A61P29/00 , C07K14/705 , C07K16/28 , A61K39/395
CPC分类号： C07K14/70542 , A61K47/48469 , A61K47/48476 , A61K47/48484 , A61K47/48561 , A61K51/1027 , C07K16/2842 , Y10S514/885
摘要： A method for the treatment of inflammatory bowel disease (IBD) is disclosed. The method comprises administration of an antibody, polypeptide or other molecule recognizing VLA-4, a surface molecule expressed on most types of white blood cells and involved in leukocyte adhesion to endothelium and other tissus in the gut.
摘要翻译：公开了一种治疗炎症性肠病（IBD）的方法。该方法包括施用识别VLA-4的抗体，多肽或其他分子，在大多数类型的白细胞上表达的表面分子，并涉及白细胞粘附于肠内的内皮和其他组织。

65. 发明授权

US5792458A Mutant diphtheria toxin conjugates 失效
标题翻译：突变型白喉毒素共轭物
公开(公告)号：US5792458A
公开(公告)日：1998-08-11
申请号：US323591
申请日：1994-10-17
申请人： Virginia G. Johnson , Larry Greenfield , Richard J. Youle , Walter Laird
发明人： Virginia G. Johnson , Larry Greenfield , Richard J. Youle , Walter Laird
IPC分类号： A61K38/00 , A61K47/48 , C07K14/34 , C12N9/00 , A61K38/16 , A61K39/395 , A61K39/44
CPC分类号： A61K47/483 , A61K47/48484 , A61K47/48592 , A61K47/48623 , C07K14/34 , A61K38/00 , Y10S424/832
摘要： A potent and specific immunotoxin is prepared by coupling an inactivated diphtheria toxin to a binding moiety such as a monoclonal antibody or transferrin. The immunotoxins are specific for human tumors and leukemias and are indistinguishable in cell toxicity from that of the native toxin linked to the binding domain without the toxicity to other cells. The immunotoxin is useful in treating graft versus host disease as well as selectively killing tumor cells, such as medulloblastoma and glioblastoma cells.
摘要翻译：通过将灭活的白喉毒素偶联至结合部分如单克隆抗体或转铁蛋白来制备有效和特异性的免疫毒素。免疫毒素对于人类肿瘤和白血病是特异性的，并且与与结合结构域连接的天然毒素的细胞毒性无差异，而对其它细胞没有毒性。免疫毒素可用于治疗移植物抗宿主病以及选择性地杀死肿瘤细胞，例如成神经管细胞瘤和成胶质细胞瘤细胞。

66. 发明授权

US5208021A Method of preparing diphtheria immunotoxins 失效
标题翻译：白喉免疫毒素的制备方法
公开(公告)号：US5208021A
公开(公告)日：1993-05-04
申请号：US301376
申请日：1989-01-25
申请人： Virginia G. Johnson , Larry Greenfield , Richard J. Youle , Walter Laird
发明人： Virginia G. Johnson , Larry Greenfield , Richard J. Youle , Walter Laird
IPC分类号： A61K38/00 , A61K47/48 , C07K14/34
CPC分类号： A61K47/483 , A61K47/48484 , A61K47/48592 , A61K47/48623 , C07K14/34 , A61K38/00 , Y10S530/82
摘要： A potent and specific immunotoxin is prepared by coupling an inactivated diphteria toxin to a binding moiety such as a monoclonal antibody or transferrin. The immunotoxins are specific for human tumors and leukemias and are indistinguishable in cell toxicity from that of the native toxin linked to the binding domain without the toxicity to other cells. The immunotoxin is useful in treating graft versus host disease as well as selectively killing tumor cells, such as medulloblastoma and glioblastoma cells.
摘要翻译：通过将灭活的二倍体毒素偶联至结合部分如单克隆抗体或转铁蛋白来制备有效和特异性的免疫毒素。免疫毒素对于人类肿瘤和白血病是特异性的，并且与与结合结构域连接的天然毒素的细胞毒性无差异，而对其它细胞没有毒性。免疫毒素可用于治疗移植物抗宿主病以及选择性地杀死肿瘤细胞，例如成神经管细胞瘤和成胶质细胞瘤细胞。

67. 发明授权

US5082927A Selectively cytotoxic IL-4-PE40 fusion protein 失效
标题翻译：选择性细胞毒性IL-4-PE40融合蛋白
公开(公告)号：US5082927A
公开(公告)日：1992-01-21
申请号：US351448
申请日：1989-05-12
申请人： Ira Pastan , David FitzGerald , Masato Ogata
发明人： Ira Pastan , David FitzGerald , Masato Ogata
IPC分类号： A61K38/00 , A61K39/00 , A61K47/48 , C07K14/21 , C07K14/495 , C07K14/55 , C07K16/28
CPC分类号： C07K14/495 , A61K47/48369 , A61K47/48484 , C07K14/21 , C07K14/55 , C07K16/2866 , C07K16/2896 , A61K38/00 , A61K39/00 , C07K2319/00 , C07K2319/55 , C07K2319/75 , Y10S530/82 , Y10S530/825
摘要： The present invention provides a chimeric protein IL4-PE40 which selectively kills IL4 receptor bearing cells. A mutant form of the protein is also provided.
摘要翻译：本发明提供了选择性地杀死携带IL4受体的细胞的嵌合蛋白IL4-PE40。还提供了蛋白质的突变体形式。

68. 发明授权

US4664911A Immunotoxin conjugates employing toxin B chain moieties 失效
标题翻译：使用毒素B链部分的免疫毒素结合物
公开(公告)号：US4664911A
公开(公告)日：1987-05-12
申请号：US506540
申请日：1983-06-21
申请人： Jonathan W. Uhr , Ellen S. Vitetta
发明人： Jonathan W. Uhr , Ellen S. Vitetta
IPC分类号： A61K39/395 , A61K39/00 , A61K39/40 , A61K47/48 , G01N33/53 , G01N33/554 , G01N33/563
CPC分类号： A61K47/48484 , A61K47/48446 , Y10S436/813 , Y10S436/819 , Y10S530/866
摘要： Compositions and methods for potentiating the cytotoxic activity of immunogotoxin conjugates are provided. The compositions of the present invention include a selective binding agent such as an antibody coupled to a toxin B chain moiety such as ricin B chain.
摘要翻译：提供了增强免疫毒素缀合物的细胞毒活性的组合物和方法。本发明的组合物包括选择性结合剂，例如与毒素B链部分偶联的抗体，例如蓖麻毒素B链。

69. 发明授权

US4638049A Antitumor protein hybrid and process for the preparation thereof 失效
标题翻译：抗肿瘤蛋白杂交体及其制备方法
公开(公告)号：US4638049A
公开(公告)日：1987-01-20
申请号：US137193
申请日：1980-04-04
申请人： Yasuhiko Masuho , Takeshi Hara , Teruhisa Noguchi
发明人： Yasuhiko Masuho , Takeshi Hara , Teruhisa Noguchi
IPC分类号： A61K39/395 , A61K35/74 , A61K47/48 , A61P35/00 , A61P43/00 , C07K15/14
CPC分类号： A61K47/48715 , A61K38/16 , A61K47/48484 , C07K16/3061 , C07K2317/55 , C07K2319/55 , Y10S530/866
摘要： Antitumor protein hybrid, composed of a moiety which is substantially the fragment Fab of an antitumor immunoglobulin and a moiety which is substantially the fragment A of a diphtheria toxin, which is expressed by the following formula (I):Fab--S.sub.1 --(X).sub.n --S.sub.2 --FA).sub.m (I)(where Fab indicates a moiety which is substantially the fragment Fab of an antitumor immunoglobulin; FA indicates a moiety which is substantially the fragment A of a diphtheria toxin; X indicates a divalent organic radical; S.sub.1 and S.sub.2 are both sulfur atoms, S.sub.1 indicating a sulfur atom arising from the disulfide bond (--S--S-- bond) in an immunoglobulin and S.sub.2 a sulfur atom arising from the disulfide bond in a diphtheria toxin; n stands for 0 to 1 and m stands for an integer of 1 to 5). This antitumor protein hybrid has remarkable and specific cytotoxicity against tumor cells, e.g., in mice.
摘要翻译：由下式（I）表示的基本上是抗肿瘤免疫球蛋白片段Fab的部分和基本上是白喉毒素片段A的部分组成的抗肿瘤蛋白质杂交体：Fab-S1-（X） n-S2-FA）m（I）（其中Fab表示基本上为抗肿瘤免疫球蛋白的片段Fab的部分; FA表示基本上为白喉毒素片段A的部分; X表示二价有机基团; S1 和S2都是硫原子，S1表示在免疫球蛋白中由二硫键（-SS-键）产生的硫原子，S2表示在白喉毒素中由二硫键产生的硫原子; n表示0至1，m表示为1〜5的整数）。这种抗肿瘤蛋白质杂交体对肿瘤细胞具有显着和特异性的细胞毒性，例如在小鼠中。

70. 发明授权

US4379145A Antitumor protein hybrid and process for the preparation thereof 失效
标题翻译：抗肿瘤蛋白杂交体及其制备方法
公开(公告)号：US4379145A
公开(公告)日：1983-04-05
申请号：US216709
申请日：1980-12-15
申请人： Yasuhiko Masuho , Naoji Umemoto , Takeshi Hara , Hidematsu Hirai
发明人： Yasuhiko Masuho , Naoji Umemoto , Takeshi Hara , Hidematsu Hirai
IPC分类号： C07K14/195 , A61K35/74 , A61K39/395 , A61K47/48 , A61P35/00 , C07K1/113 , C07K14/00 , C07K14/41 , C07K16/00 , C07K19/00 , A61K37/00 , C07C103/52 , C07G7/00
CPC分类号： A61K47/48684 , A61K47/48484 , C07K16/303 , C07K2319/55
摘要： Antitumor protein hybrid, having a moiety consisting of the antitumor immunoglobulin and a moiety substantially consisting of the fragment A of a diphtheria toxin, which is expressed by the following formula (I):Ab(NHCO--X--S.sub.1 --S.sub.2 --FA).sub.n (I)(where Ab indicates a moiety consisting of the antitumor immunoglobulin and FA indicates a moiety substantially consisting of the fragment A of a diphtheria toxin; X is an alkylene group or phenylene group which either has or does not have a branching of 1 to 5 carbon atoms. N in the amido bond is a nitrogen atom arising from the amino group in the antitumor immunoglobulin; S.sub.1 and S.sub.2 are both sulfur atoms, S.sub.2 indicating a sulfur atom arising from the disulfide bond in a diphtheria toxin; n stands for an integer of 1 to 5).This antitumor protein hybrid has remarkable and specific citotoxicity against tumor cells.
摘要翻译：具有由抗肿瘤免疫球蛋白组成的部分和基本上由白喉毒素片段A组成的部分的抗肿瘤蛋白质杂交体，其由下式（I）表示：Ab（NHCO-X-S1-S2-FA）n （I）（其中Ab表示由抗肿瘤免疫球蛋白组成的部分，FA表示基本上由白喉毒素片段A组成的部分; X是亚烷基或亚苯基，其具有或不具有1至 5个碳原子，氨基键中的N是由抗肿瘤免疫球蛋白氨基产生的氮原子; S1和S2都是硫原子，S2表示在白喉毒素中由二硫键产生的硫原子; n代表 1〜5的整数）。该抗肿瘤蛋白杂合物对肿瘤细胞具有显着的特异性宿主毒性。

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