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1. 发明申请

US20070297977A1 Tumor Necrosis Factor-Gamma 有权
标题翻译：肿瘤坏死因子 - 伽玛
公开(公告)号：US20070297977A1
公开(公告)日：2007-12-27
申请号：US11837082
申请日：2007-08-10
申请人： Guo-Liang Yu , Jian Ni , Craig Rosen , Jun Zhang
发明人： Guo-Liang Yu , Jian Ni , Craig Rosen , Jun Zhang
IPC分类号： A61K51/00 , A61K39/395 , A61P29/00
CPC分类号： A61K51/08 , C07K16/241 , Y10S930/144
摘要： Human TNF-gamma-alpha and TNF-gamma-beta polypeptides and DNA (RNA) encoding such polypeptides and a procedure for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing such polypeptides to inhibit cellular growth, for example in a tumor or cancer, for facilitating wound-healing, to provide resistance against infection, induce inflammatory activities, and stimulating the growth of certain cell types to treat diseases, for example restenosis. Also disclosed are diagnostic methods for detecting a mutation in the TNF-gamma-alpha and TNF-gamma-beta nucleic acid sequences or overexpression of the TNF-gamma-alpha and/or TNF-gamma-beta polypeptides. Antagonists against such polypeptides and their use as a therapeutic to treat cachexia, septic shock, cerebral malaria, inflammation, arthritis and graft-rejection are also disclosed.
摘要翻译：公开了人类TNF-γ-α和TNF-γ-β多肽和编码这种多肽的DNA（RNA）以及通过重组技术产生此类多肽的方法。还公开了利用这些多肽抑制细胞生长的方法，例如在肿瘤或癌症中，用于促进伤口愈合，提供抗感染，诱导炎症活性和刺激某些细胞类型的生长以治疗疾病，示例再狭窄。还公开了用于检测TNF-γ-α和TNF-γ-β核酸序列中的突变或TNF-γ-α和/或TNF-γ-β多肽的过表达的诊断方法。还公开了抗这些多肽的拮抗剂及其作为治疗性恶病质，败血性休克，脑疟疾，炎症，关节炎和移植排斥的治疗剂的用途。

2. 发明授权

US07118750B1 Modified TNF-alpha molecules, DNA encoding such and vaccines comprising such modified TNF-alpha and DNA 失效
标题翻译：修饰的TNF-α分子，编码这样的DNA和包含这种修饰的TNF-α和DNA的疫苗
公开(公告)号：US07118750B1
公开(公告)日：2006-10-10
申请号：US09060294
申请日：1998-04-15
申请人： Martin Roland Jensen , Søren Mouritsen , Henrik Elsner , Iben Dalum
发明人： Martin Roland Jensen , Søren Mouritsen , Henrik Elsner , Iben Dalum
IPC分类号： A61K38/19 , C07K14/25
CPC分类号： C07K14/525 , A61K38/00 , A61K39/00 , C07K19/00 , C07K2319/00 , Y10S930/144
摘要： A modified human TNFα molecule is capable of raising neutralizing antibodies towards unmodified human TNFα following administration of the modified TNFα to a human host, wherein one or more peptide fragments of the human TNFα molecule has been substituted by one or more peptides containing immunodominant T cell epitopes or a truncated form of the molecule containing the immunodominant epitope and one or both flanking regions of the human TNFα-molecule containing at least one TNFα B cell epitope, wherein the substitution introduces a substantial change in the amino acid sequence of any one of the strands of the front β-sheet, in any one of the connecting loops, or in any one of the B′, I, or D strands of the back β-sheet.
摘要翻译：在将修饰的TNFα施用于人宿主后，经修饰的人TNFα分子能够提供针对未修饰的人TNFα的中和抗体，其中人TNFα分子的一个或多个肽片段已被含有免疫优势T细胞表位的一种或多种肽取代或包含免疫显性表位和含有至少一种TNFαb细胞表位的人TNFα分子的一个或两个侧翼区域的分子的截短形式，其中所述取代引入任何一条链的氨基酸序列的显着变化在任何一个连接环中，或在背面β片中的任何一个B'，I或D链中的前β片。

3. 发明申请

US20020169118A1 TNF receptors, TNF binding proteins and DNAs coding for them 审中-公开
公开(公告)号：US20020169118A1
公开(公告)日：2002-11-14
申请号：US09899429
申请日：2001-07-03
申请人： Amgen, Inc.
发明人： Rudolf Hauptmann , Adolf Himmler , Ingrid Maurer-Fogy , Christian Stratowa
IPC分类号： A61K038/17
CPC分类号： G01N33/57484 , A61K38/00 , C07K14/7151 , C12Q1/6886 , C12Q2600/136 , G01N33/6863 , Y02A50/473 , Y10S930/12 , Y10S930/144
摘要： DNA sequences coding for a TNF-binding protein and for the TNF receptor of which this protein constitutes the soluble domain. The DNA sequences can be used for preparing recombinant DNA molecules in order to produce TNF-binding protein and TNF receptor. Recombinant TNF-binding protein is used in pharmaceutical preparations for treating indications in which TNF has a harmful effect. With the aid of the TNF receptor or fragments thereof or with the aid of suitable host organisms transformed with recombinant DNA molecules containing the DNA which codes for the TNF receptor or fragments or modifications thereof, it is possible to investigate substances for their interaction with the TNF receptor and/or for their effect on the biological activity of TNF.

4. 发明授权

US06294352B1 TNF receptors, TNF binding proteins and DNAs coding for them 失效
标题翻译： TNF受体，TNF结合蛋白和编码它们的DNA
公开(公告)号：US06294352B1
公开(公告)日：2001-09-25
申请号：US08383676
申请日：1995-02-01
申请人： Rudolf Hauptmann , Adolf Himmler , Ingrid Maurer-Fogy , Christian Stratowa
发明人： Rudolf Hauptmann , Adolf Himmler , Ingrid Maurer-Fogy , Christian Stratowa
IPC分类号： C12N1500
CPC分类号： G01N33/57484 , A61K38/00 , C07K14/7151 , C12Q1/6886 , C12Q2600/136 , G01N33/6863 , Y02A50/473 , Y10S930/12 , Y10S930/144
摘要： DNA sequences coding for a TNF-binding protein and for the TNF receptor of which this protein constitutes the soluble domain. The DNA sequence can be used for preparing recombinant DNA molecules in order to produce TNF-binding protein and TNF receptor. Recombinant TNF-binding protein is used in pharmaceutical preparations for treating indications in which TNF has a harmful effect. With the aid of the TNF receptor or fragments thereof or with the aid of suitable host organisms transformed with recombinant DNA molecules containing the DNA which codes for the TNF receptor or fragments or modifications thereof, it is possible to investigate substances for their interaction with the TNF receptor and/or for their effect on the biological activity of TNF.
摘要翻译：编码TNF结合蛋白的DNA序列和该蛋白质构成可溶性结构域的TNF受体。 DNA序列可用于制备重组DNA分子，以产生TNF结合蛋白和TNF受体。重组TNF结合蛋白用于治疗TNF具有有害作用的适应症的药物制剂中。借助于TNF受体或其片段或借助含有编码TNF受体的DNA的重组DNA分子或其片段或修饰物转化的合适的宿主生物，可以研究它们与TNF相互作用的物质受体和/或其对TNF的生物活性的影响。

5. 发明授权

US5889156A TNF deletion muteins 失效
标题翻译： TNF缺失突变蛋白
公开(公告)号：US5889156A
公开(公告)日：1999-03-30
申请号：US449689
申请日：1995-05-24
申请人： Michael Kriegler , Carl F. Perez
发明人： Michael Kriegler , Carl F. Perez
IPC分类号： C12N5/10 , A01N63/00 , A61K9/50 , A61K35/76 , A61K38/00 , A61K38/19 , A61K38/21 , A61K38/22 , A61K48/00 , A61P35/00 , C07K14/47 , C07K14/525 , C07K14/57 , C12N5/08 , C12N5/22 , C12N7/00 , C12N15/09 , C12N15/19 , C12N15/23 , C12N15/28 , C12N15/48 , C12N15/867 , C12P21/02 , C12R1/91 , C12R1/92
CPC分类号： A61K9/5184 , A61K38/191 , A61K38/21 , C07K14/525 , C07K14/57 , C12N15/86 , C07K2319/02 , C12N2740/13043 , C12N2740/13052 , Y10S930/144
摘要： A virion expression system for a desired protein packaged in an envelope derived from a retrovirus useful in administering proteins which cross cell membranes in order to serve their function. Preferred virions are those that carry an RNA sequence that encodes cytokines or lymphokines, and includes IL-2, multiple drug resistance protein, and TNF.
摘要翻译：用于所需蛋白质的病毒体表达系统，其包装在源自逆转录病毒的包膜中，所述反转录病毒可用于施用跨越细胞膜的蛋白质以便发挥其功能。优选的病毒粒子是携带编码细胞因子或淋巴因子的RNA序列的病毒粒子，并且包括IL-2，多重耐药性蛋白质和TNF。

6. 发明授权

US5874077A Human til cells expressing recombinant TNF prohormone 失效
标题翻译：表达重组TNF激素原的人类细胞
公开(公告)号：US5874077A
公开(公告)日：1999-02-23
申请号：US448889
申请日：1995-05-24
申请人： Michael Kriegler , Carl F. Perez
发明人： Michael Kriegler , Carl F. Perez
IPC分类号： C12N5/10 , A01N63/00 , A61K9/50 , A61K35/76 , A61K38/00 , A61K38/19 , A61K38/21 , A61K38/22 , A61K48/00 , A61P35/00 , C07K14/47 , C07K14/525 , C07K14/57 , C12N5/08 , C12N5/22 , C12N7/00 , C12N15/09 , C12N15/19 , C12N15/23 , C12N15/28 , C12N15/48 , C12N15/867 , C12P21/02 , C12R1/91 , C12R1/92 , A61K45/05
CPC分类号： A61K9/5184 , A61K38/191 , A61K38/21 , C07K14/525 , C07K14/57 , C12N15/86 , C07K2319/02 , C12N2740/13043 , C12N2740/13052 , Y10S930/144
摘要： Tumor Infiltrating Lymphocyte (TIL) cells transformed with exogenous DNA encoding tumor necrosis factor (TNF) prohormone variants are disclosed. Among such variants are the TNF .gamma. sig construct, which facilitates expression of the mature TNF polypeptide, and the noncleavable cytotoxic prohormone variants TNF.DELTA.(1.fwdarw.12) and TNF(1+12). The transformed TIL cells are useful in antitumor therapy.
摘要翻译：公开了用编码肿瘤坏死因子（TNF）激素原变体的外源DNA转化的肿瘤浸润性淋巴细胞（TIL）细胞。在这些变体中，TNFγsig构建体促进成熟TNF多肽的表达，以及不可修复的细胞毒性激素原变体TNF-α（1→12）和TNF（1 + 12）。转化的TIL细胞可用于抗肿瘤治疗。

7. 发明授权

US5157106A N-terminal deletions of lymphotoxin, their preparation and use 失效
标题翻译： LYMPHOTOXIN的N-末端残基，其制备和使用
公开(公告)号：US5157106A
公开(公告)日：1992-10-20
申请号：US61439
申请日：1987-06-15
申请人： Klaus Schollmeier , Achim Moeller , Wolfgang Koerwer , Thomas Doerper , Heinz Hillen , Lothar Daum , Franz Emling , Gerhard Keilhauer
发明人： Klaus Schollmeier , Achim Moeller , Wolfgang Koerwer , Thomas Doerper , Heinz Hillen , Lothar Daum , Franz Emling , Gerhard Keilhauer
IPC分类号： C07K14/52 , A61K38/00 , A61P35/00 , C07K14/00 , C07K14/525 , C12N15/00 , C12N15/09 , C12P21/02 , C12R1/19
CPC分类号： C07K14/525 , A61K38/00 , Y10S530/82 , Y10S930/143 , Y10S930/144
摘要： Polypeptides which differ from lymphotoxin by the absence of amino acids at the N-terminal end of the lymphotoxin are described. The polypeptides can be prepared by gene manipulation and are suitable, alone or in combination with lymphokines, as pharmaceuticals.
摘要翻译：描述了通过在淋巴毒素的N-末端不存在氨基酸而与淋巴毒素不同的多肽。多肽可以通过基因操作制备，并且单独或与淋巴因子组合适合作为药物。

8. 发明授权

US4677063A Human tumor necrosis factor 失效
标题翻译：人类肿瘤坏死因子
公开(公告)号：US4677063A
公开(公告)日：1987-06-30
申请号：US760661
申请日：1985-07-30
申请人： David F. Mark , Alice M. Wang , Martha B. Ladner , Abla A. Creasey , Leo S. Lin , Janelle Van Arsdell
发明人： David F. Mark , Alice M. Wang , Martha B. Ladner , Abla A. Creasey , Leo S. Lin , Janelle Van Arsdell
IPC分类号： A61K38/00 , C07K14/525 , C12P21/00 , A61K39/00 , C12N1/00 , C12N15/00
CPC分类号： C07K14/525 , A61K38/00 , Y10S530/808 , Y10S930/144
摘要： Human tumor necrosis factor (TNF) has been prepared using recombinant methods. A human promyelocytic leukemia cell line has been induced using an improved induction procedure, and the TNF purified to homogeneity. Methods, vectors, and cells useful in obtaining human TNF in practical amounts are disclosed. Muteins having N-terminal deletions, which muteins have superior biological activity, are also disclosed.
摘要翻译：人肿瘤坏死因子（TNF）已经使用重组方法制备。已经使用改进的诱导程序诱导人类早幼粒细胞白血病细胞系，并且将TNF纯化至均匀。公开了用于实际获得人TNF的方法，载体和细胞。还公开了具有N-末端缺失的突变蛋白，其突变蛋白具有优异的生物活性。

9. 发明授权

US4360458A Antitumor antibacterial agents 失效
标题翻译：抗肿瘤抗菌剂
公开(公告)号：US4360458A
公开(公告)日：1982-11-23
申请号：US122626
申请日：1980-03-06
申请人： Hideo Koshiyama , Fumihide Sakai , Hiroaki Ohkuma
发明人： Hideo Koshiyama , Fumihide Sakai , Hiroaki Ohkuma
IPC分类号： A61K38/00 , C07K7/06 , C07C103/52 , A61K37/00 , C07G7/00
CPC分类号： C12R1/01 , C07K7/06 , A61K38/00 , Y10S930/144 , Y10S930/19 , Y10S930/27
摘要： An antitumor antibacterial complex referred to as BBM-928 is described which is produced by microbiological fermentation under controlled conditions using a species of actinomycetes. The bioactive components of the complex have pronounced antitumor activity and are moderately to weakly active against gram-positive and acid fast bacteria but practically inactive against gram-negative bacteria and fungi. Based on median survival time, the component designated BBM-928A is substantially more active than mitomycin C by a factor of 10 to 300 fold against intraperitoneally implanted mouse tumors.
摘要翻译：描述了称为BBM-928的抗肿瘤抗菌复合物，其通过微生物发酵在受控条件下使用放线菌种生产。该复合物的生物活性成分具有显着的抗肿瘤活性，对革兰氏阳性和酸性快速细菌具有中等至弱的活性，但对革兰氏阴性细菌和真菌几乎无活性。基于中位生存时间，针对腹膜内植入的小鼠肿瘤，指定为BBM-928A的组分比丝裂霉素C活性要高10至300倍。

10. 发明授权

US08163522B1 Human TNF receptor 失效
标题翻译：人类TNF受体
公开(公告)号：US08163522B1
公开(公告)日：2012-04-24
申请号：US08444791
申请日：1995-05-19
申请人： Manfred Brockhaus , Reiner Gentz , Dembic Zlatko , Werner Lesslauer , Hansruedi Lotscher , Ernst-Jurgen Schlaeger
发明人： Manfred Brockhaus , Reiner Gentz , Dembic Zlatko , Werner Lesslauer , Hansruedi Lotscher , Ernst-Jurgen Schlaeger
IPC分类号： C12N15/12 , C12N15/63 , C12N5/10 , C12P21/00
CPC分类号： C07K14/7151 , C07K16/2866 , C12N2799/026 , Y10S930/144
摘要： The present invention is concerned with non-soluble proteins and soluble or insoluble fragments thereof, which bind TNF, in homogeneous form, as well as their physiologically compatible salts, especially those proteins having a molecular weight of about 55 or 75 kD (non-reducing SDS-PAGE conditions), a process for the isolation of such proteins, antibodies against such proteins, DNA sequences which code for non-soluble proteins and soluble or non-soluble fragments thereof, which bind TNF, as well as those which code for proteins comprising partly of a soluble fragment, which binds TNF, and partly of all domains except the first of the constant region of the heavy chain of human immunoglobulins and the recombinant proteins coded thereby as well as a process for their manufacture using transformed pro- and eukaryotic host cells.
摘要翻译：本发明涉及不溶性蛋白质及其可溶性或不溶性片段，其以均质形式结合TNF，以及它们的生理相容性盐，特别是分子量为约55或75kD的蛋白质（非还原型 SDS-PAGE条件），分离这些蛋白质的方法，针对这些蛋白质的抗体，编码结合TNF的不溶性蛋白质的DNA序列和可溶性或非可溶性片段，以及编码蛋白质的蛋白质其部分包含结合TNF的可溶性片段，以及部分除了人免疫球蛋白重链的恒定区域的第一个区域以外的所有结构域，以及由此编码的重组蛋白质以及其使用转化的真核和真核生物的方法宿主细胞。

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