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公开(公告)号：US20090275137A1
公开(公告)日：2009-11-05
申请号：US12494458
申请日：2009-06-30
CPC分类号： C07K14/7051 , C12N5/0636 , C12N15/1037 , C12N2510/00 , C40B40/02 , G01N33/56972 , G01N33/68 , G01N33/6842 , G01N33/6854 , G01N2333/39 , G01N2333/7051
摘要： T cell receptors (TCRS) that have higher affinity for a ligand than wild type TCRs are provided. These high affinity TCRs are formed by mutagenizing a T cell receptor protein coding sequence to generate a variegated population of mutants of the T cell receptor protein coding sequence; transforming the T cell receptor mutant coding sequence into yeast cells; inducing expression of the T cell receptor mutant coding sequence on the surface of yeast cells; and selecting those cells expressing T cell receptor mutants that have higher affinity for the peptide/MHC ligand than the wild type T cell receptor protein. The high affinity TCRs can be used in place of an antibody or single chain antibody.
摘要翻译： 提供了比野生型TCR对配体具有更高亲和力的T细胞受体（TCRS）。 通过诱变T细胞受体蛋白质编码序列产生T细胞受体蛋白编码序列突变体的杂色群体，形成这些高亲和性TCR。 将T细胞受体突变体编码序列转化为酵母细胞; 在酵母细胞表面诱导T细胞受体突变体编码序列的表达; 并选择那些表达与野生型T细胞受体蛋白相比对肽/ MHC配体具有更高亲和力的T细胞受体突变体的细胞。 高亲和性TCR可用于代替抗体或单链抗体。
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22.发明申请公开(公告)号：US20080249008A1
公开(公告)日：2008-10-09
申请号：US11725695
申请日：2007-03-20
IPC分类号： A61K38/18 , C07K14/485 , A61P35/00 , A61P25/00 , A61K48/00 , C40B30/04 , C12P21/00 , A61P9/00 , A61P17/02 , C07H21/00
CPC分类号： C07K14/485 , A61K38/00
摘要： The present invention is based, in part, on our discovery that EGF can be engineered to generate mutants that bind to the EGF receptor (EGFR) of a cell and that have a desirable effect on the activity of the cell. For example, the mutants can agonize the receptor (i.e., increase a biological activity of the receptor), or antagonize the receptor (i.e., decrease or inhibit a biological activity of the receptor). In turn, the rate at which the cell proliferates, for example, can be changed. Moreover, some of these mutants bind EGFR with a higher affinity than wild-type EGF exhibits. The affinity may increase by about, for example, 2-, 5-, 10-, 15-, 20-, 25-, 30-, 50-, or 100-fold relative to wild-type EGF.
摘要翻译： 本发明部分基于我们的发现，EGF可以被工程化以产生结合细胞的EGF受体（EGFR）的突变体，并且对细胞的活性具有期望的影响。 例如，突变体可以激动受体（即，增加受体的生物活性）或拮抗受体（即降低或抑制受体的生物活性）。 反过来，细胞增殖的速度例如可以改变。 此外，这些突变体中的一些以比野生型EGF显示更高的亲和力结合EGFR。 相对于野生型EGF，亲和力可以增加约例如2-，5-，10-，15-，20-，25-，30-，50-或100倍。
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公开(公告)号：US07232888B2
公开(公告)日：2007-06-19
申请号：US10609671
申请日：2003-07-01
IPC分类号： C07K16/00
CPC分类号： C07K16/3007 , A61K2039/505 , C07K16/00 , C07K16/005 , C07K2317/24 , C07K2317/565 , C07K2317/622
摘要： The present invention relates to improved antibodies against tumor surface antigens and their use in the treatment of tumors. Of particular interest are highly stable, humanized, high affinity antibodies against carcinoembryonic antigen (CEA), especially the antibody we have termed sm3E, which is derived from the scFv antibody MFE-23. Such antibodies have the potential for improved therapeutic efficacy.
摘要翻译： 本发明涉及抗肿瘤表面抗原的改进抗体及其在治疗肿瘤中的用途。 特别令人感兴趣的是高度稳定的，人源化的，高亲和力的针对癌胚抗原（CEA）的抗体，特别是源自scFv抗体MFE-23的称为sm3E的抗体。 这样的抗体具有改善治疗功效的潜力。
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公开(公告)号：US06696251B1
公开(公告)日：2004-02-24
申请号：US09724108
申请日：2000-11-28
申请人： K. Dane Wittrup , David M. Kranz , Michele Kieke , Eric T. Boder
发明人： K. Dane Wittrup , David M. Kranz , Michele Kieke , Eric T. Boder
IPC分类号： C12Q168
CPC分类号： C07K14/705 , C12N15/1037 , C40B40/02 , G01N33/68 , G01N33/6854 , G01N2333/39
摘要： The present invention provides a genetic method for tethering polypeptides to the yeast cell wall in a form accessible for binding to macromolecules. Combining this method with fluorescence-activated cell sorting provides a means of selecting proteins with increased or decreased affinity for another molecule, altered specificity, or conditional binding. Also provided is a method for genetic fusion of the N terminus of a polypeptide of interest to the C-terminus of the yeast Aga2p cell wall protein. The outer wall of each yeast cell can display approximately 104 protein agglutinins. The native agglutinins serve as specific adhesion contacts to fuse yeast cells of opposite mating type during mating. In effect, yeast has evolved a platform for protein-protein binding without steric hindrance from cell wall components. As one embodiment, attaching an scFv antibody fragment to the Aga2p agglutinin effectively mimics the cell surface display of antibodies by B cells in the immune system for affinity maturation in vivo. As another embodiment, T cell receptor mutants can be isolated by this method that are efficiently displayed on the yeast cell surface, providing a means of altering T cell receptor binding affinity and specificity by library screening.
摘要翻译： 本发明提供了一种遗传方法，用于以能够与大分子结合的形式将多肽连接到酵母细胞壁。 将该方法与荧光激活细胞分选相结合提供了选择具有增加或降低的对另一分子的亲和力，改变的特异性或条件结合的蛋白质的方法。 还提供了目的多肽的N末端与酵母Aga2p细胞壁蛋白的C末端的遗传融合的方法。 每个酵母细胞的外壁可显示约10 4个蛋白质凝集素。 天然凝集素用作特异性粘附接触，以在交配期间融合相反交配型的酵母细胞。 实际上，酵母已经发展出蛋白质 - 蛋白质结合的平台，而没有来自细胞壁组分的空间位阻。 作为一个实施方案，将scFv抗体片段连接到Aga2p凝集素上有效地模拟了免疫系统中B细胞的抗体的细胞表面显示，用于体内的亲和力成熟。 作为另一个实施方案，可以通过这种方法分离T细胞受体突变体，其有效地显示在酵母细胞表面上，提供通过文库筛选来改变T细胞受体结合亲和力和特异性的方法。
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公开(公告)号：US06423538B1
公开(公告)日：2002-07-23
申请号：US09724297
申请日：2000-11-28
申请人： K. Dane Wittrup , David M. Kranz , Michele Keike , Eric T. Boder
发明人： K. Dane Wittrup , David M. Kranz , Michele Keike , Eric T. Boder
IPC分类号： C12N1581
CPC分类号： C12N15/1037 , C40B40/02 , G01N33/68 , G01N33/6854 , G01N2333/39
摘要： The present invention provides a genetic method for tethering polypeptides to the yeast cell wall in a form accessible for binding to macromolecules. Combining this method with fluorescence-activated cell sorting provides a means of selecting proteins with increased or decreased affinity for another molecule, altered specificity, or conditional binding. Also provided is a method for genetic fusion of the N terminus of a polypeptide of interest to the C-terminus of the yeast Aga2p cell wall protein. The outer wall of each yeast cell can display approximately 104 protein agglutinins. The native agglutinins serve as specific adhesion contacts to fuse yeast cells of opposite mating type during mating. If effect, yeast has evolved a platform for protein-protein binding without steric hindrance from cell wall components. As one embodiment, attaching an scFv antibody fragment to the Aga2p agglutinin effectively mimics the cell surface display of antibodies by B cells in the immune system for affinity maturation in vivo. As another embodiment, T cell receptor mutants can be isolated by this method that are efficiently displayed on the yeast cell surface, providing a means of altering T cell receptor binding affinity and specificity by library screening.
摘要翻译： 本发明提供了一种遗传方法，用于以能够与大分子结合的形式将多肽连接到酵母细胞壁。 将该方法与荧光激活细胞分选相结合提供了选择具有增加或降低的对另一分子的亲和力，改变的特异性或条件结合的蛋白质的方法。 还提供了目的多肽的N末端与酵母Aga2p细胞壁蛋白的C末端的遗传融合的方法。 每个酵母细胞的外壁可以显示大约104个蛋白质凝集素。 天然凝集素用作特异性粘附接触，以在交配期间融合相反交配型的酵母细胞。 如果发挥作用，酵母已经发展出蛋白质 - 蛋白质结合的平台，没有细胞壁组分的空间位阻。 作为一个实施方案，将scFv抗体片段连接到Aga2p凝集素上有效地模拟了免疫系统中B细胞的抗体的细胞表面显示，用于体内的亲和力成熟。 作为另一个实施方案，可以通过这种方法分离T细胞受体突变体，其有效地显示在酵母细胞表面上，提供通过文库筛选来改变T细胞受体结合亲和力和特异性的方法。
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公开(公告)号：US08815237B2
公开(公告)日：2014-08-26
申请号：US12746411
申请日：2008-12-05
IPC分类号： A61K39/395
CPC分类号： C07K16/283 , C07K2317/41
摘要： The present invention is based, in part, on our discovery of immunoglobulins (e.g., immunoglobulin G (IgG)) polypeptides (e.g., murine or human IgG, such as human IgG1) that are aglycosylated yet retain the ability to bind to an Fc receptor, such as an activating Fc receptor (e.g., FcγRIIA and/or FcγRIIIA).
摘要翻译： 本发明部分地基于我们发现免疫球蛋白（例如，免疫球蛋白G（IgG））多糖（例如，鼠或人IgG，例如人IgG1），其被糖基化，但仍具有结合Fc受体的能力 ，例如活化的Fc受体（例如FcγRIIA和/或FcγRIIIA）。
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公开(公告)号：US20110091412A1
公开(公告)日：2011-04-21
申请号：US12741552
申请日：2008-11-05
申请人： K. Dane Wittrup , David V. Liu
发明人： K. Dane Wittrup , David V. Liu
IPC分类号： A61K38/20 , C07K14/55 , A61K31/7105 , A61K31/7088 , C07H21/00 , C12N15/63 , C12N5/10 , A61K35/12 , A61P35/00 , A61P31/18
CPC分类号： C07K14/55
摘要： The present invention relates to mutant IL-2 polypeptides that act as receptor antagonists. The mutant IL-2 polypeptides bind CD 25 but do not activate the IL-2 receptor. Also provided are methods of using the mutant IL-2 polypeptides, for example, to treat a patient who has cancer or a viral infection. The mutant polypeptides can also be used in various delivery systems.
摘要翻译： 本发明涉及作为受体拮抗剂的突变型IL-2多肽。 突变体IL-2多肽结合CD25但不激活IL-2受体。 还提供了使用突变IL-2多肽的方法，例如，治疗患有癌症或病毒感染的患者。 突变体多肽也可用于各种递送系统。
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公开(公告)号：US20100254987A1
公开(公告)日：2010-10-07
申请号：US12715162
申请日：2010-03-01
申请人： Kelly J. DAVIS , K. Dane Wittrup
发明人： Kelly J. DAVIS , K. Dane Wittrup
CPC分类号： C07K16/44 , A61K2039/505 , C07K16/3007 , C07K2299/00 , C07K2317/31 , C07K2317/32 , C07K2317/41 , C07K2317/622 , C07K2317/77 , C07K2317/92 , C07K2319/00
摘要： The present invention features, inter alia, compositions and methods for the treatment of cancer and infectious disease. The compositions include engineered proteins that specifically bind a metal chelate and may be bispecific. For example, the engineered proteins may bind (a) a target (e.g., a cellular protein) on a cancerous cell or a pathogen and (b) a metal chelate comprising DOTA, or an active variant thereof, and a metal ion such as a radionuclide. By virtue of the multiple binding sites, the engineered protein effectively delivers a metal chelate to a cell one wishes to destroy.
摘要翻译： 本发明尤其涉及用于治疗癌症和感染性疾病的组合物和方法。 组合物包括特异性结合金属螯合物并可以是双特异性的工程蛋白。 例如，工程改造的蛋白质可以结合（a）癌细胞或病原体上的靶（例如，细胞蛋白），和（b）包含DOTA或其活性变体的金属螯合物和金属离子如 放射性核素 由于多重结合位点，工程蛋白质有效地将金属螯合物递送到希望破坏的细胞。
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公开(公告)号：US20100221248A1
公开(公告)日：2010-09-02
申请号：US12605273
申请日：2009-10-23
IPC分类号： A61K39/395 , C07K14/705 , C07K16/28 , C07H21/04 , C12N15/63 , C12N5/00 , A61P35/04
CPC分类号： C07K16/30 , C07K14/705 , C07K16/283 , C07K2317/33 , C07K2317/92 , C07K2318/20 , C07K2319/24 , C07K2319/35
摘要： The present invention features engineered proteins that include a first polypeptide that specifically binds a first target (e.g., a cellular target, such as a cell-surface antigen) and a second polypeptide that selectively binds an activating FcR.
摘要翻译： 本发明的特征在于包括特异性结合第一靶（例如细胞靶，例如细胞表面抗原）的第一多肽和选择性结合活化的FcR的第二多肽的工程蛋白。
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公开(公告)号：US20100036097A1
公开(公告)日：2010-02-11
申请号：US12535083
申请日：2009-08-04
IPC分类号： C07K14/55
CPC分类号： C07K14/55 , A61K38/00 , G01N33/6869 , G01N2333/55 , G01N2500/04
摘要： The present invention relates to IL-2 mutants with increased affinity for the IL-2 alpha-receptor subunit (IL-2Rα). The invention thus includes IL-2 mutants with improved biological potency. The invention also includes methods for directed evolution of IL-2α using yeast surface display to generate mutants with increased affinity for IL-2Rα.
摘要翻译： 本发明涉及对IL-2α受体亚单位（IL-2Rα）具有增加的亲和力的IL-2突变体。 因此，本发明包括具有改善的生物效能的IL-2突变体。 本发明还包括用于使用酵母表面显示产生IL-2α的定向进化以产生具有增加的对IL-2Rα的亲和力的突变体的方法。
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