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1. 发明申请

US20120270797A1 ENGINEERED PROTEINS INCLUDING MUTANT FIBRONECTIN DOMAINS 审中-公开
标题翻译：包括突变体蛋白质域的工程蛋白质
公开(公告)号：US20120270797A1
公开(公告)日：2012-10-25
申请号：US13390086
申请日：2010-08-13
申请人： Karl Dane Wittrup , Jamie B. Spangler , Benjamin Joseph Hackel
发明人： Karl Dane Wittrup , Jamie B. Spangler , Benjamin Joseph Hackel
IPC分类号： C07K19/00 , C12N15/62 , C12N15/63 , C12N1/19 , A61P35/00 , C12N1/21 , C12N5/10 , C12N9/96 , A61K38/17
CPC分类号： C07K14/78 , A61K38/00 , C07K2318/20
摘要： The present invention features engineered proteins that can include a genetically modified Fn domain; two or more such domains joined to one another; or at least one genetically modified Fn domain joined to a target-specific protein scaffold. One or more accessory sequences can be included in or added to any of these configurations. Methods of use, including methods of treating cancer, with the engineered proteins are also disclosed.
摘要翻译：本发明的特征在于可以包括遗传修饰的Fn结构域的工程蛋白质; 两个或更多个这样的域彼此连接; 或至少一个连接到靶特异性蛋白质支架的遗传修饰的Fn结构域。一个或多个附件序列可以包括在这些配置中或添加到这些配置中的任一个中。还公开了使用方法，包括治疗癌症的方法与工程改造的蛋白质。

2. 发明申请

US20130216543A1 ANTIBODY-BASED CONSTRUCTS DIRECTED AGAINST TYROSINE KINASE RECEPTORS 有权
标题翻译：针对酪氨酸激酶受体指导的基于抗体的构建体
公开(公告)号：US20130216543A1
公开(公告)日：2013-08-22
申请号：US13817525
申请日：2011-08-20
申请人： Karl Dane Wittrup , Jamie B. Spangler , Benjamin E. Epstein , Brian L. Ross
发明人： Karl Dane Wittrup , Jamie B. Spangler , Benjamin E. Epstein , Brian L. Ross
IPC分类号： C07K16/28
CPC分类号： C07K16/2863 , C07K2317/31 , C07K2317/35 , C07K2317/60 , C07K2317/76 , C07K2319/00
摘要： The present invention features antibody-based constructs that include a combination of two or more of a tetrameric antibody, a single chain antibody, a diabody, a triabody, another immunoglobulin-based moiety, as described herein, or biologically active variants thereof.
摘要翻译：本发明的特征在于基于抗体的构建体，其包括如本文所述的四聚体抗体，单链抗体，双抗体，三体抗体，另一个基于免疫球蛋白的部分中的两种或更多种的组合或其生物活性变体。

3. 发明授权

US09464136B2 Antibody-based constructs directed against tyrosine kinase receptors 有权
标题翻译：针对酪氨酸激酶受体的基于抗体的构建体
公开(公告)号：US09464136B2
公开(公告)日：2016-10-11
申请号：US13817525
申请日：2011-08-20
申请人： Karl Dane Wittrup , Jamie B. Spangler , Benjamin E. Epstein , Brian L. Ross
发明人： Karl Dane Wittrup , Jamie B. Spangler , Benjamin E. Epstein , Brian L. Ross
IPC分类号： C07K16/28 , A61K39/395
CPC分类号： C07K16/2863 , C07K2317/31 , C07K2317/35 , C07K2317/60 , C07K2317/76 , C07K2319/00
摘要： The present invention features antibody-based constructs that include a combination of two or more of a tetrameric antibody, a single chain antibody, a diabody, a triabody, another immunoglobulin-based moiety, as described herein, or biologically active variants thereof.
摘要翻译：本发明的特征在于基于抗体的构建体，其包括如本文所述的四聚体抗体，单链抗体，双抗体，三体抗体，另一个基于免疫球蛋白的部分中的两种或更多种的组合或其生物活性变体。

4. 发明申请

US20140080766A1 COMPOSITIONS AND METHODS FOR MACROMOLECULAR DRUG DELIVERY 审中-公开
标题翻译：用于大分子药物递送的组合物和方法
公开(公告)号：US20140080766A1
公开(公告)日：2014-03-20
申请号：US13978072
申请日：2012-01-07
申请人： Christopher Michael Pirie , David Victor Liu , Nicole Jie Yeon Yang , Karl Dane Wittrup
发明人： Christopher Michael Pirie , David Victor Liu , Nicole Jie Yeon Yang , Karl Dane Wittrup
IPC分类号： A61K47/48 , A61K31/713
CPC分类号： A61K47/62 , A61K31/713 , A61K47/6825 , A61K47/6849 , A61K47/6853
摘要： The present invention features compositions and methods for delivering a therapeutic agent to the cytoplasm of a cell. We have developed, inter alia, a system in which two or more distinct moieties—at least one therapeutic moiety and at least one potentiating moiety—selectively target and specifically bind cell surface molecules that are then internalized to an intracellular, membrane-bound compartment, such as an endosome. In some embodiments, as discussed further below, a third moiety that induces clustering of the targeted cell surface molecule can also be employed. Regardless of whether the compositions and methods include two or three moieties, the therapeutic agent can be any agent one wishes to deliver to the cytoplasm of a cell, and the potentiating agent can be any agent that destabilizes the intracellular, sub-cellular compartment in which the therapeutic agent is sequestered. The potentiating moiety can include, for example, a lytic agent (i.e., an agent that lyses or otherwise increases the permeability of the membrane of the intracellular compartment containing the therapeutic agent). To direct the various moieties of the system, including the therapeutic, potentiating, and clustering moieties, to a selected cellular target, any of the moieties can include a binding agent that selectively targets and specifically binds a molecule present on the surface of the targeted cell.
摘要翻译：本发明的特征在于将治疗剂递送至细胞的细胞质的组合物和方法。我们特别开发了一种系统，其中两个或多个不同部分 - 至少一个治疗部分和至少一个增强部分 - 选择性地靶向并特异性结合细胞表面分子，然后细胞内分泌到胞内膜结合的隔室，如内体。在一些实施方案中，如下文进一步讨论的，也可以使用诱导靶细胞表面分子聚集的第三部分。不管组合物和方法是否包括两个或三个部分，治疗剂可以是希望递送至细胞的细胞质的任何试剂，并且增效剂可以是使细胞内，亚细胞隔室不稳定的任何试剂，其中治疗剂被隔离。增强部分可以包括例如溶解剂（即，裂解或以其它方式增加含有治疗剂的细胞内隔室的膜的渗透性的试剂）。为了将系统的各个部分（包括治疗性，增强和聚集部分）引导至所选择的细胞靶，任何部分可以包括选择性靶向和特异性结合存在于靶细胞表面上的分子的结合剂。

5. 发明授权

US08349311B2 Mutant interleukin-2 (IL-2) polypeptides 有权
标题翻译：突变型白细胞介素-2（IL-2）多肽
公开(公告)号：US08349311B2
公开(公告)日：2013-01-08
申请号：US13088045
申请日：2011-04-15
申请人： Karl Dane Wittrup , Balaji M. Rao , Douglas A. Lauffenburger
发明人： Karl Dane Wittrup , Balaji M. Rao , Douglas A. Lauffenburger
IPC分类号： A61K38/20 , 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。

6. 发明授权

US08648176B2 Engineered proteins with high affinity for DOTA chelates 有权
标题翻译：对DOTA螯合物具有高亲和力的工程化蛋白质
公开(公告)号：US08648176B2
公开(公告)日：2014-02-11
申请号：US12715162
申请日：2010-03-01
申请人： Kelly Davis Orcutt , Karl Dane Wittrup
发明人： Kelly Davis Orcutt , Karl Dane Wittrup
IPC分类号： C07K16/00
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。

7. 发明授权

US08450247B2 Cell display libraries 有权
标题翻译：单元格显示库
公开(公告)号：US08450247B2
公开(公告)日：2013-05-28
申请号：US11051481
申请日：2005-02-07
申请人： Beau R. Peelle , Angela M. Belcher , Karl Dane Wittrup , Eric Krauland
发明人： Beau R. Peelle , Angela M. Belcher , Karl Dane Wittrup , Eric Krauland
IPC分类号： C40B20/00 , C40B30/00 , C40B40/02 , C07K14/00 , C07K7/00
CPC分类号： C12N15/1037 , G01N33/569
摘要： Eukaryotic cell display libraries for use in panning processes comprising expressed biomolecules for specific and selective binding and enrichment to solid material surfaces including, for example, metal, magnetic, and semiconducting surfaces. Display can be regulated. Peptide and protein display on yeast cells are preferred. Solid materials can be fabricated in the presence of cell display libraries which have been subjected to panning against the solid materials. Nanoparticles can be grown in the presence of the biomolecules from reactive precursors. The nanoparticles can show quantum confinement effects. Self-healing films can be prepared.
摘要翻译：用于淘选方法的真核细胞展示文库包括用于特异性和选择性结合和富集固体材料表面的表达生物分子，包括例如金属，磁性和半导体表面。显示可以调节。酵母细胞上的肽和蛋白质显示是优选的。在已经对固体材料进行淘洗的细胞显示库的存在下，可以制备固体材料。纳米颗粒可以在活性前体的生物分子存在下生长。纳米粒子可以显示量子限制效应。自愈膜可以准备好。

8. 发明授权

US5773245A Methods for increasing secretion of overexpressed proteins 失效
标题翻译：增加过表达蛋白质分泌的方法
公开(公告)号：US5773245A
公开(公告)日：1998-06-30
申请号：US441139
申请日：1995-05-15
申请人： Karl Dane Wittrup , Anne Skaja Robinson
发明人： Karl Dane Wittrup , Anne Skaja Robinson
IPC分类号： C07K14/39 , C07K14/395 , C12N9/90 , C12N15/12 , C12N15/31 , C12N15/61 , C12N15/81 , C12P21/02 , C12N15/67
CPC分类号： C12N15/81 , C07K14/39 , C07K14/395 , C12N9/90 , C12P21/02
摘要： The present invention is directed to methods for increasing secretion of an overexpressed gene product present in a host cell, by inducing expression of chaperone proteins within the host cell.
摘要翻译：本发明涉及通过在宿主细胞内诱导分子伴侣蛋白的表达来增加存在于宿主细胞中的过表达基因产物的分泌的方法。

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