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1. 发明授权

US08679771B2 Specific N-terminal labeling of peptides and proteins in complex mixtures 有权
标题翻译：复杂混合物中肽和蛋白质的特异性N末端标记
公开(公告)号：US08679771B2
公开(公告)日：2014-03-25
申请号：US12524557
申请日：2008-01-24
申请人： James A. Wells , Sami Mahrus
发明人： James A. Wells , Sami Mahrus
IPC分类号： G01N33/535
CPC分类号： G01N33/6803 , C12Q1/34
摘要： This invention provides general methods for selective labeling of proteins on their N-termini with synthetic peptides. The methods of this invention can be applied to the global proteomic profiling of complex mixtures of proteins and polypeptides.
摘要翻译：本发明提供了用合成肽在其N-末端上选择性标记蛋白质的一般方法。本发明的方法可以应用于蛋白质和多肽的复合物混合物的全局蛋白质组学分析。

2. 发明授权

US09493522B2 Discovery of candidate biomarkers of in vivo apoptosis by global profiling of caspase cleavage sites 有权
标题翻译：通过胱天蛋白酶切割位点的全局分析发现候选生物标志物的体内凋亡
公开(公告)号：US09493522B2
公开(公告)日：2016-11-15
申请号：US13016710
申请日：2011-01-28
申请人： James A. Wells , Sami Mahrus
发明人： James A. Wells , Sami Mahrus
IPC分类号： G01N31/00 , G01N33/53 , C07K14/47 , C12Q1/37 , G01N33/573 , G01N33/574 , G01N33/68
CPC分类号： C07K14/47 , C07K14/4747 , C12Q1/37 , G01N33/573 , G01N33/574 , G01N33/6848 , G01N2333/96466 , G01N2510/00
摘要： The present invention relates to the discovery of novel biomarkers of in vivo apoptosis based on a large number of caspase-like cleavage sites. These biomarkers are useful for detection and quantification of apoptosis in a biological sample. The invention also provides synthetic peptides and proteins corresponding to neo-epitopes created by proteolytic processing of these cleavage sites. The synthetic peptides can be used as standards to enable identification and quantitation of these biomarkers using mass spectrometry. The synthetic proteins can be used to generate antibodies and other binding reagents specific for these biomarkers. Methods for detecting apoptosis as well as for diagnosing or for providing a prognosis for a disease or disease state characterized by apoptosis are also provided herein. Finally, the invention provides compositions and kits for performing the methods of the invention.
摘要翻译：本发明涉及基于大量胱天蛋白酶样切割位点发现体内细胞凋亡的新生物标志物。这些生物标志物可用于检测和定量生物样品中的细胞凋亡。本发明还提供了对应于通过这些切割位点的蛋白水解加工产生的新表位的合成肽和蛋白质。合成肽可以用作标准物，以便能够使用质谱鉴定和定量这些生物标志物。合成蛋白质可用于产生对这些生物标志物特异性的抗体和其他结合试剂。本文还提供了检测细胞凋亡以及用于诊断或提供特征为凋亡的疾病或疾病状态的预后的方法。最后，本发明提供了用于实施本发明方法的组合物和试剂盒。

3. 发明申请

US20100143912A1 SPECIFIC N-TERMINAL LABELING OF PEPTIDES AND PROTEINS IN COMPLEX MIXTURES 有权
标题翻译：复合混合物中肽和蛋白质的特异性N-末端标记
公开(公告)号：US20100143912A1
公开(公告)日：2010-06-10
申请号：US12524557
申请日：2008-01-24
申请人： James A. Wells , Sami Mahrus
发明人： James A. Wells , Sami Mahrus
IPC分类号： C12Q1/68 , C12P21/06 , C12Q1/37
CPC分类号： G01N33/6803 , C12Q1/34
摘要： This invention provides general methods for selective labeling of proteins on their N-termini with synthetic peptides. The methods of this invention can be applied to the global proteomic profiling of complex mixtures of proteins and polypeptides.
摘要翻译：本发明提供了用合成肽在其N-末端上选择性标记蛋白质的一般方法。本发明的方法可以应用于蛋白质和多肽的复合物混合物的全局蛋白质组学分析。

4. 发明申请

US20120028266A1 DISCOVERY OF CANDIDATE BIOMARKERS OF IN VIVO APOPTOSIS BY GLOBAL PROFILING OF CASPASE CLEAVAGE SITES 有权
标题翻译：通过CASPASE CLEAVAGE SITES的全球分析发现病毒性生物标志物
公开(公告)号：US20120028266A1
公开(公告)日：2012-02-02
申请号：US13016710
申请日：2011-01-28
申请人： James A. Wells , Sami Mahrus
发明人： James A. Wells , Sami Mahrus
IPC分类号： G01N33/566 , C07K7/06 , C12Q1/00 , C07K16/18 , G01N33/577 , C12Q1/37 , C07K14/47 , C07K7/08
CPC分类号： C07K14/47 , C07K14/4747 , C12Q1/37 , G01N33/573 , G01N33/574 , G01N33/6848 , G01N2333/96466 , G01N2510/00
摘要： The present invention relates to the discovery of novel biomarkers of in vivo apoptosis based on a large number of caspase-like cleavage sites. These biomarkers are useful for detection and quantification of apoptosis in a biological sample. The invention also provides synthetic peptides and proteins corresponding to neo-epitopes created by proteolytic processing of these cleavage sites. The synthetic peptides can be used as standards to enable identification and quantitation of these biomarkers using mass spectrometry. The synthetic proteins can be used to generate antibodies and other binding reagents specific for these biomarkers. Methods for detecting apoptosis as well as for diagnosing or for providing a prognosis for a disease or disease state characterized by apoptosis are also provided herein. Finally, the invention provides compositions and kits for performing the methods of the invention.
摘要翻译：本发明涉及基于大量胱天蛋白酶样切割位点发现体内细胞凋亡的新生物标志物。这些生物标志物可用于检测和定量生物样品中的细胞凋亡。本发明还提供了对应于通过这些切割位点的蛋白水解加工产生的新表位的合成肽和蛋白质。合成肽可以用作标准物，以便能够使用质谱鉴定和定量这些生物标志物。合成蛋白质可用于产生对这些生物标志物特异性的抗体和其他结合试剂。本文还提供了检测细胞凋亡以及用于诊断或提供特征为凋亡的疾病或疾病状态的预后的方法。最后，本发明提供了用于实施本发明方法的组合物和试剂盒。

5. 发明授权

US08685893B2 Phage display 有权
标题翻译：噬菌体展示
公开(公告)号：US08685893B2
公开(公告)日：2014-04-01
申请号：US12181222
申请日：2008-07-28
申请人： Sachdev S. Sidhu , Gregory A. Weiss , James A. Wells
发明人： Sachdev S. Sidhu , Gregory A. Weiss , James A. Wells
IPC分类号： C40B40/02
CPC分类号： C40B40/02 , C07K14/005 , C07K2319/00 , C12N15/1037 , C12N2795/10022 , C12N2795/10043
摘要： The transformation yield of electroporation is increased by using higher DNA concentrations and DNA affinity purification. Fusion proteins of a viral coat protein variant and a heterologous polypeptide are useful in phage display systems.
摘要翻译：通过使用更高的DNA浓度和DNA亲和纯化，提高了电穿孔的转化产率。病毒外壳蛋白变体和异源多肽的融合蛋白可用于噬菌体展示系统。

6. 发明申请

US20120328628A1 ANTIBODIES TO CONFORMATIONALLY TRAPPED PROTEINS 审中-公开
标题翻译：抗体以一致性捕获蛋白
公开(公告)号：US20120328628A1
公开(公告)日：2012-12-27
申请号：US12307906
申请日：2007-07-06
申请人： James A. Wells , Junjun Gao
发明人： James A. Wells , Junjun Gao
IPC分类号： C07K1/00 , C07H21/04 , C07H21/02 , C07K16/00 , C07K2/00 , A61K38/02 , A61K39/395 , A61K31/7105 , A61K31/711 , C07K1/14 , A61K39/00 , A61P25/16 , A61P35/00 , A61P25/00 , A61P9/10 , A61P29/00 , A61P31/00 , C40B30/04 , G01N33/566 , C07H1/00
CPC分类号： G01N33/68 , C07K16/40 , C07K2299/00 , C07K2317/55 , C07K2317/565 , C07K2317/92 , G01N33/6845 , G01N33/6848 , G01N2500/00
摘要： The present invention provides methods for generating antibodies to specific conformations of proteins. The conformation specific antibodies of the invention can be put to a variety of uses including diagnosis and treatment of diseases and for screening for compounds that induce conformational changes in proteins upon binding.
摘要翻译：本发明提供了产生针对特定蛋白质构象的抗体的方法。本发明的构象特异性抗体可以用于各种用途，包括疾病的诊断和治疗以及用于筛选在结合时诱导蛋白质构象变化的化合物。

7. 发明授权

US07375193B2 Anti-VEGF antibodies 有权
标题翻译：抗VEGF抗体
公开(公告)号：US07375193B2
公开(公告)日：2008-05-20
申请号：US11537015
申请日：2006-09-29
申请人： Manuel Baca , James A. Wells , Leonard G. Presta , Henry B. Lowman , Yvonne Man-Yee Chen
发明人： Manuel Baca , James A. Wells , Leonard G. Presta , Henry B. Lowman , Yvonne Man-Yee Chen
IPC分类号： C07K16/00
CPC分类号： C07K16/22 , C07K2317/24 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/73 , C07K2317/76 , C07K2317/92
摘要： Humanized and variant anti-VEGF antibodies and various uses therefor are disclosed. The anti-VEGF antibodies have strong binding affinities for VEGF; inhibit VEGF-induced proliferation of endothelial cells in vitro; and inhibit tumor growth in vivo.
摘要翻译：公开了人源化和变异的抗VEGF抗体及其各种用途。抗VEGF抗体对VEGF具有很强的结合亲和力; 体外抑制VEGF诱导的内皮细胞增殖; 并在体内抑制肿瘤生长。

8. 发明授权

US06197927B1 Peptide variants of protein A 失效
标题翻译：蛋白A的肽变体
公开(公告)号：US06197927B1
公开(公告)日：2001-03-06
申请号：US09036549
申请日：1998-03-06
申请人： Andrew C. Braisted , Melissa A. Starovasnik , James A. Wells
发明人： Andrew C. Braisted , Melissa A. Starovasnik , James A. Wells
IPC分类号： C07K512
CPC分类号： C07K14/31 , C07K2319/00 , Y10S436/828
摘要： Z domain variants of staphylococcal protein A have significantly reduced size but possess IgG-binding affinity equivalent to the wild type Z domain. These Z domain variants are suitable for use in affinity chromatography purification of proteins and in the treatment of staphylococcic diseases.
摘要翻译：葡萄球菌蛋白A的Z结构域变体具有显着减小的大小，但具有与野生型Z结构域相当的IgG结合亲和力。这些Z结构域变体适用于蛋白质的亲和层析纯化和葡萄球菌性疾病的治疗。

9. 发明授权

US6057292A Method for inhibiting growth hormone action 失效
标题翻译：抑制生长激素作用的方法
公开(公告)号：US6057292A
公开(公告)日：2000-05-02
申请号：US28587
申请日：1998-02-24
申请人： Brian C. Cunningham , Henry B. Lowman , James A. Wells , Ross G. Clark , Kenneth Olson , Germaine G. Fuh
发明人： Brian C. Cunningham , Henry B. Lowman , James A. Wells , Ross G. Clark , Kenneth Olson , Germaine G. Fuh
IPC分类号： C12N15/09 , A61K31/00 , A61K38/00 , A61K38/27 , A61K47/48 , A61P3/00 , A61P3/10 , A61P5/00 , A61P5/08 , A61P5/12 , A61P13/12 , A61P35/00 , A61P37/00 , A61P43/00 , C07K1/107 , C07K14/61 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/18 , C12N15/63 , C12P21/02 , C12R1/19
CPC分类号： A61K47/48215 , C07K14/61 , A61K38/00 , C07K2319/00 , Y10S514/866 , Y10S930/12
摘要： Human growth hormone variants are disclosed having enhanced affinity for the growth hormone receptor. Also disclosed are human growth hormone variants conjugated to one or more chemical groups, such as poly(ethylene glycol), which is believed to prolong the in vivo half-life of the variants.
摘要翻译：公开了对生长激素受体具有增强的亲和力的人生长激素变体。还公开了与一种或多种化学基团缀合的人生长激素变体，例如聚（乙二醇），其被认为延长了变体的体内半衰期。

10. 发明授权

US06013478A Method for identifying active domains and amino acid residues in polypeptides and hormone variants 失效
标题翻译：用于鉴定多肽和激素变体中活性结构域和氨基酸残基的方法
公开(公告)号：US06013478A
公开(公告)日：2000-01-11
申请号：US104036
申请日：1998-06-24
申请人： James A. Wells , Brian C. Cunningham
发明人： James A. Wells , Brian C. Cunningham
IPC分类号： A61K38/24 , C07K1/00 , C07K14/575 , C07K14/61 , C07K16/00 , C12N1/21 , C12N15/00 , C12N15/16 , C12N15/18 , C12N15/63 , C12P21/06 , C12Q1/68 , G01N33/48 , G01N33/50 , G01N33/53 , G01N33/566 , G06F19/00
CPC分类号： C07K14/575 , C12N15/1058 , Y10S530/806 , Y10S530/808
摘要： The invention provides methods for the systematic analysis of the structure and function of polypeptides by identifying active domains which influence the activity of the polypeptide with a target substance. Such active domains are determined by substituting selected amino acid segments of the polypeptide with an analogous polypeptide segment from an analog to the polypeptide. The analog has a different activity with the target substance as compared to the parent polypeptide. The activities of the segment-substituted polypeptides are compared to the same activity for the parent polypeptide for the target. A comparison of such activities provides an indication of the location of the active domain in the parent polypeptide. The invention also provides methods for identifying the active amino acid residues within the active domain of the parent polypeptide. The method comprises substituting a scanning amino acid for one of the amino acid residues within the active domain of the parent polypeptide and assaying the residue-substituted polypeptide so formed with a target substance. The invention further provides polypeptide variants comprising segment-substituted and residue-substituted growth hormones, prolactins and placental lactogens.
摘要翻译：本发明提供了通过鉴定影响多肽与靶物质的活性的活性结构域来系统分析多肽的结构和功能的方法。通过用类似物与多肽的类似多肽片段取代多肽的选定氨基酸片段来确定此类活性结构域。与亲本多肽相比，类似物与目标物质具有不同的活性。将段取代的多肽的活性与目标的亲本多肽的相同活性进行比较。这些活性的比较提供了活性结构域在亲本多肽中的位置的指示。本发明还提供鉴定亲本多肽活性结构域内活性氨基酸残基的方法。该方法包括用扫描氨基酸取代母体多肽的活性结构域内的氨基酸残基之一，并测定与靶物质形成的残基取代的多肽。本发明还提供了包含片段取代的和残基取代的生长激素，催乳素和胎盘乳糖的多肽变体。

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