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1. 发明授权

US09249231B2 Motif-specific and context-independent antibodies that specifically bind to a cleaved caspase motif 有权
标题翻译：与特异性结合切割的半胱天冬酶基序的母体特异性和上下文相关抗体
公开(公告)号：US09249231B2
公开(公告)日：2016-02-02
申请号：US13289651
申请日：2011-11-04
申请人： Michael Comb , Ailan Guo , John Edward Rush, II , Jun-Ming Cai , Jing Li , Jing Zhou
发明人： Michael Comb , Ailan Guo , John Edward Rush, II , Jun-Ming Cai , Jing Li , Jing Zhou
IPC分类号： C07K16/44 , C07K16/00 , C12N5/07
CPC分类号： C07K16/18 , C07K16/44 , C07K2317/14 , C07K2317/20 , C07K2317/33 , C07K2317/34
摘要： There is provided a motif-specific, context-independent antibody that specifically binds a recurring, modified motif consisting of (i) at least one sumoylated lysine residue, and (ii) one or more degenerate amino acids bound by a peptide bond to said sumoylated lysine residue, said antibody specifically binding said motif in a plurality of non-homologous peptides or proteins within an organism in which it recurs. Also provided is a motif-specific, context-independent antibody that specifically binds a recurring, modified motif consisting of (i) a C-terminal aspartic acid residue, and (ii) one or more degenerate amino acids bound by a peptide bond to said C-terminal aspartic acid residue, said antibody specifically binding said motif in a plurality of non-homologous peptides or proteins within an organism in which it recurs.
摘要翻译：提供了一种特异性基因，独立于上下文的抗体，其特异性结合由（i）至少一个sumoylated赖氨酸残基组成的复发性修饰基序，和（ii）通过肽键与所述sumoylated结合的一个或多个简并氨基酸赖氨酸残基，所述抗体特异性结合所述基序在其再次发生的生物体内的多个非同源肽或蛋白质中。还提供了一种特异性基因，独立于上下文的抗体，其特异性结合由（i）C末端天冬氨酸残基组成的重复修饰基序，和（ii）一个或多个与肽键结合的简并氨基酸与所述 C末端天冬氨酸残基，所述抗体特异性结合所述基序在其再次发生的生物体内的多个非同源肽或蛋白质中。

2. 发明申请

US20120208985A1 Motif-Specific and Context-Independent Antibodies That Specifically Bind to a Cleaved Caspase Motif or a Sumoylated Lysine-Containing Motif 有权
标题翻译：特异性和上下文独立的抗体，其特异性结合到切割的半胱天冬酶母体或含有Sumoylated赖氨酸的基序
公开(公告)号：US20120208985A1
公开(公告)日：2012-08-16
申请号：US13289651
申请日：2011-11-04
申请人： Michael Comb , Ailan Guo , John Edward Rush, II , Jun-Ming Cai , Jing Li , Jing Zhou
发明人： Michael Comb , Ailan Guo , John Edward Rush, II , Jun-Ming Cai , Jing Li , Jing Zhou
IPC分类号： C07K16/00
CPC分类号： C07K16/18 , C07K16/44 , C07K2317/14 , C07K2317/20 , C07K2317/33 , C07K2317/34
摘要： There is provided a motif-specific, context-independent antibody that specifically binds a recurring, modified motif consisting of (i) at least one sumoylated lysine residue, and (ii) one or more degenerate amino acids bound by a peptide bond to said sumoylated lysine residue, said antibody specifically binding said motif in a plurality of non-homologous peptides or proteins within an organism in which it recurs. Also provided is a motif-specific, context-independent antibody that specifically binds a recurring, modified motif consisting of (i) a C-terminal aspartic acid residue, and (ii) one or more degenerate amino acids bound by a peptide bond to said C-terminal aspartic acid residue, said antibody specifically binding said motif in a plurality of non-homologous peptides or proteins within an organism in which it recurs.
摘要翻译：提供了一种特异性基因，独立于上下文的抗体，其特异性结合由（i）至少一个sumoylated赖氨酸残基组成的复发性修饰基序，和（ii）通过肽键与所述sumoylated结合的一个或多个简并氨基酸赖氨酸残基，所述抗体特异性结合所述基序在其再次发生的生物体内的多个非同源肽或蛋白质中。还提供了一种特异性基因，独立于上下文的抗体，其特异性结合由（i）C末端天冬氨酸残基组成的重复修饰基序，和（ii）一个或多个与肽键结合的简并氨基酸与所述 C末端天冬氨酸残基，所述抗体特异性结合所述基序在复制的生物体内的多个非同源肽或蛋白质。

3. 发明申请

US20110045603A1 Serine, Threonine, and Tyrosine Phosphorylation Sites 审中-公开
标题翻译：丝氨酸，苏氨酸和酪氨酸磷酸化位点
公开(公告)号：US20110045603A1
公开(公告)日：2011-02-24
申请号：US12763886
申请日：2010-04-20
申请人： Ailan Guo , Albrecht Moritz , Anthony Possemato , Ting-Lei Gu , Jian Yu , Charles Lawrence Farnsworth , Corinne Michaud , Hong Ren , Jessica Ann Cherry , Jing Zhou , Valerie Lee Goss , Erik Spek , Yu Li , Meghan Ann Tucker , John Edward Rush, II , Matthew Stokes , Klarisa Rikova
发明人： Ailan Guo , Albrecht Moritz , Anthony Possemato , Ting-Lei Gu , Jian Yu , Charles Lawrence Farnsworth , Corinne Michaud , Hong Ren , Jessica Ann Cherry , Jing Zhou , Valerie Lee Goss , Erik Spek , Yu Li , Meghan Ann Tucker , John Edward Rush, II , Matthew Stokes , Klarisa Rikova
IPC分类号： G01N33/53 , C07K16/18
CPC分类号： C07K16/18 , C07K14/47 , C07K16/44 , G01N33/6842
摘要： The invention discloses 990 novel phosphorylation sites identified in carcinoma and leukemia, peptides (including AQUA peptides) comprising a phosphorylation site of the invention, antibodies specifically bind to a novel phosphorylation site of the invention, and diagnostic and therapeutic uses of the above.
摘要翻译：本发明公开了在癌和白血病中鉴定的990个新的磷酸化位点，包含本发明的磷酸化位点的肽（包括AQUA肽），特异性结合本发明的新的磷酸化位点的抗体，以及上述的诊断和治疗用途。

4. 发明申请

US20110111424A1 ANALYSIS OF UBIQUITINATED POLYPEPTIDES 审中-公开
标题翻译：不饱和聚酯的分析
公开(公告)号：US20110111424A1
公开(公告)日：2011-05-12
申请号：US12967284
申请日：2010-12-14
申请人： John Edward Rush, II , Jing Li , Ailan Guo
发明人： John Edward Rush, II , Jing Li , Ailan Guo
IPC分类号： G01N33/53 , C07K16/00
CPC分类号： C07K16/00 , G01N33/6842 , G01N2440/36
摘要： The invention relates to antibody reagents that specifically bind to peptides carrying a ubiquitin remnant from a digested or chemically treated biological sample. The reagents allow the technician to identify ubiquitinated polypeptides as well as the sites of ubiquitination on them. The reagents are preferably employed in proteomic analysis using mass spectrometry. The antibody reagents specifically bind to the remnant of ubiquitin (i.e., a diglycine modified epsilon amine of lysine) left on a peptide which as been generated by digesting or chemically treating ubiquitinated proteins. The inventive antibody reagents' affinity to the ubiquitin remnant does not depend on the remaining amino acid sequences flanking the modified (i.e., ubiquitinated) lysine, i.e., they are context independent.
摘要翻译：本发明涉及与经消化或经化学处理的生物样品中携带泛素残基的肽特异性结合的抗体试剂。试剂允许技术人员识别泛素化的多肽以及它们上泛素化的位点。试剂优选用于使用质谱的蛋白质组学分析。抗体试剂特异性结合残留在通过消化或化学处理泛素化蛋白质产生的肽上的泛素（即，赖氨酸的二甘氨酸修饰的ε胺）残基。本发明的抗体试剂对泛素残留物的亲和力不依赖于修饰（即泛素化）赖氨酸侧翼的剩余氨基酸序列，即它们是上下文无关的。

5. 发明申请

US20100173428A1 Protein Phosphorylation By Basophillic Serine/Threonine Kinases 审中-公开
标题翻译：蛋白磷酸化由嗜碱性丝氨酸/苏氨酸激酶
公开(公告)号：US20100173428A1
公开(公告)日：2010-07-08
申请号：US12683835
申请日：2010-01-07
申请人： Ailan Guo , Albrecht Moritz , Anthony Possemato , Charles Farnsworth , Hong Ren , Klarisa Rikova , John Edward Rush, II , Matthew Stokes , Meghan Tucker , Yu Li
发明人： Ailan Guo , Albrecht Moritz , Anthony Possemato , Charles Farnsworth , Hong Ren , Klarisa Rikova , John Edward Rush, II , Matthew Stokes , Meghan Tucker , Yu Li
IPC分类号： G01N33/53 , C07K16/18
CPC分类号： C07K16/18 , C07K16/40 , C12Q1/485 , G01N33/6872
摘要： The invention discloses 461 novel phosphorylation sites identified in basophilic Ser/Thr kinase signaling pathways, peptides (including AQUA peptides) comprising a phosphorylation site of the invention, antibodies specifically bind to a novel phosphorylation site of the invention, and diagnostic and therapeutic uses of the above.
摘要翻译：本发明公开了在嗜碱性Ser / Thr激酶信号通路中鉴定的461个新的磷酸化位点，包含本发明的磷酸化位点的肽（包括AQUA肽），特异性结合本发明的新的磷酸化位点的抗体，以及以上。

6. 发明申请

US20110104820A1 Tyrosine, Serine, And Threonine Phosphorylation Sites 审中-公开
标题翻译：酪氨酸，丝氨酸和苏氨酸磷酸化位点
公开(公告)号：US20110104820A1
公开(公告)日：2011-05-05
申请号：US12902261
申请日：2010-10-12
申请人： John Edward Rush, II , Ting-Lei Gu , Valerie Goss , Anthony Possemato
发明人： John Edward Rush, II , Ting-Lei Gu , Valerie Goss , Anthony Possemato
IPC分类号： G01N33/566 , C07K16/00
CPC分类号： C07K16/44 , C07K2317/34 , G01N33/574 , G01N33/6842
摘要： The invention discloses 94 novel phosphorylation sites identified in carcinoma and leukemia, peptides (including AQUA peptides) comprising a phosphorylation site of the invention, antibodies that specifically bind to a novel phosphorylation site of the invention, and diagnostic and therapeutic uses of the above.
摘要翻译：本发明公开了在癌和白血病中鉴定的94个新的磷酸化位点，包含本发明的磷酸化位点的肽（包括AQUA肽），特异性结合本发明的新的磷酸化位点的抗体以及上述的诊断和治疗用途。

7. 发明授权

US09920110B2 Methods and reagents for creating monoclonal antibodies 有权
公开(公告)号：US09920110B2
公开(公告)日：2018-03-20
申请号：US13416582
申请日：2012-03-09
申请人： Roberto Polakiewicz , Wan Cheung Cheung , John Edward Rush, II , Sean Andre Beausoleil
发明人： Roberto Polakiewicz , Wan Cheung Cheung , John Edward Rush, II , Sean Andre Beausoleil
IPC分类号： C07K1/14 , C07K16/00 , G01N33/50 , C07K16/08 , C07K16/18 , C07K16/44
CPC分类号： C07K16/00 , C07K16/082 , C07K16/18 , C07K16/44 , C07K2317/21 , C07K2317/56 , C07K2317/565
摘要： In some embodiments, the invention relates to methods for creating a monoclonal antibody that specifically binds to antigen. The method may start from a polyclonal population of antibodies such as a non-specific polyclonal population or a polyclonal population of antibodies that specifically bind to the antigen. The method includes obtaining nucleic acid molecules encoding heavy and light immunoglobulin chains (or variable regions thereof) of multiple immunoglobulins from an animal; obtaining mass spectra information of peptide fragments of a population of polyclonal immunoglobulins that specifically bind to an antigen of choice; comparing and/or correlating the mass spectra information of the peptide fragments of the polyclonal immunoglobulins with predicted mass spectra information of predicted amino acid sequences encoded by the nucleic acid molecules, and then assembling the heavy and light chains to create an antibody (or variable region thereof) that specifically binds to the antigen.

8. 发明申请

US20120308555A1 METHODS AND REAGENTS FOR CREATING MONOCLONAL ANTIBODIES 有权
标题翻译：创建单克隆抗体的方法和试剂
公开(公告)号：US20120308555A1
公开(公告)日：2012-12-06
申请号：US13416582
申请日：2012-03-09
申请人： Roberto Polakiewicz , Wan Cheung Cheung , John Edward Rush, II , Sean Andre Beausoleil
发明人： Roberto Polakiewicz , Wan Cheung Cheung , John Edward Rush, II , Sean Andre Beausoleil
IPC分类号： C40B20/08 , A61K39/395 , C07K16/00
CPC分类号： C07K16/00 , C07K16/082 , C07K16/18 , C07K16/44 , C07K2317/21 , C07K2317/56 , C07K2317/565
摘要： In some embodiments, the invention relates to methods for creating a monoclonal antibody that specifically binds to antigen. The method may start from a polyclonal population of antibodies such as a non-specific polyclonal population or a polyclonal population of antibodies that specifically bind to the antigen. The method includes obtaining nucleic acid molecules encoding heavy and light immunoglobulin chains (or variable regions thereof) of multiple immunoglobulins from an animal; obtaining mass spectra information of peptide fragments of a population of polyclonal immunoglobulins that specifically bind to an antigen of choice; comparing and/or correlating the mass spectra information of the peptide fragments of the polyclonal immunoglobulins with predicted mass spectra information of predicted amino acid sequences encoded by the nucleic acid molecules, and then assembling the heavy and light chains to create an antibody (or variable region thereof) that specifically binds to the antigen.
摘要翻译：在一些实施方案中，本发明涉及用于产生特异性结合抗原的单克隆抗体的方法。该方法可以从抗体的多克隆群体开始，例如非特异性多克隆群体或与抗原特异性结合的抗体的多克隆群体。该方法包括获得编码来自动物的多种免疫球蛋白的重和轻免疫球蛋白链（或其可变区）的核酸分子; 获得特异性结合所选抗原的多克隆免疫球蛋白群体的肽片段的质谱信息; 比较和/或将多克隆免疫球蛋白的肽片段的质谱信息与由核酸分子编码的预测的氨基酸序列的预测质谱信息相关联，然后组合重链和轻链以产生抗体（或可变区），其特异性结合抗原。

9. 发明授权

US09453845B2 Mass spectroscopy analysis of mutant polypeptides in biological samples 有权
标题翻译：生物样品中突变体多肽的质谱分析
公开(公告)号：US09453845B2
公开(公告)日：2016-09-27
申请号：US12931445
申请日：2011-02-01
申请人： Albrecht Moritz , John Edward Rush, II , Roberto Polakiewicz
发明人： Albrecht Moritz , John Edward Rush, II , Roberto Polakiewicz
IPC分类号： C12Q1/70 , B01D59/44 , H01J49/00 , G01N15/06 , G01N33/00 , G01N33/48 , G01N33/53 , G01N33/68
CPC分类号： G01N33/6848 , B01D15/12 , B01D15/325 , B01D15/3809 , B01D15/3823 , B01D15/422 , G01N30/7233 , G01N2560/00 , G01N2570/00 , H01J49/00
摘要： The invention relates to a method for determining the presence of at least one distinct polypeptide in a biological sample comprising contacting the biological sample with a hydrolyzing agent, wherein the hydrolyzing agent is capable of hydrolyzing the distinct polypeptide in a sequence-specific manner such that at least one distinct peptide having a predetermined peptide measured accurate mass would result if the at least one distinct polypeptide were present in the biological sample, to obtain a hydrolyzed sample; bringing the hydrolyzed sample in contact with a substrate comprising at least one immobilized binding partner, wherein the at least one immobilized binding partner is capable of specifically binding the distinct peptide; removing the hydrolyzed sample from the substrate in a manner such that the distinct peptide would remain bound to the immobilized binding partner; contacting the substrate with an elution solution, wherein the distinct peptide would dissociate from the immobilized binding partner into the elution solution; subjecting a portion of the elution solution to liquid chromatography to segregate a plurality of molecules in the portion of the elution solution to obtain sorted molecules; determining the measured accurate mass of at least one sorted molecule present in the elution solution; and determining the presence of the at least one distinct polypeptide in the biological sample when a measured accurate mass of at least one molecule is substantially equal to the predetermined peptide measured accurate mass.
摘要翻译：本发明涉及一种用于确定生物样品中至少一种不同多肽的存在的方法，包括使生物样品与水解试剂接触，其中水解试剂能够以序列特异性方式水解不同的多肽，如果至少一种不同的多肽存在于生物样品中，则得到具有测定精确质量的预定肽的至少一种不同的肽，以获得水解样品; 使水解的样品与包含至少一个固定的结合配偶体的底物接触，其中至少一个固定的结合配偶体能够特异性结合不同的肽; 以使得不同的肽保持与固定的结合配偶体结合的方式从底物中除去水解的样品; 使所述底物与洗脱溶液接触，其中所述不同的肽将从固定的结合配偶体解离成洗脱溶液; 使洗脱溶液的一部分进行液相色谱分离洗脱溶液部分中的多个分子，得到分选的分子; 确定洗脱溶液中存在的至少一种分选分子的测量精确质量; 以及当所测量的至少一个分子的精确质量基本上等于所测量的精确质量的预定肽时，确定生物样品中至少一种不同多肽的存在。

10. 发明申请

US20110244445A1 Mass spectroscopy analysis of mutant polypeptides in biological samples 有权
标题翻译：生物样品中突变体多肽的质谱分析
公开(公告)号：US20110244445A1
公开(公告)日：2011-10-06
申请号：US12931445
申请日：2011-02-01
申请人： Albrecht Moritz , John Edward Rush, II , Roberto Polakiewicz
发明人： Albrecht Moritz , John Edward Rush, II , Roberto Polakiewicz
IPC分类号： G01N27/00 , C12Q1/70 , H01J49/26 , G01N33/48
CPC分类号： G01N33/6848 , B01D15/12 , B01D15/325 , B01D15/3809 , B01D15/3823 , B01D15/422 , G01N30/7233 , G01N2560/00 , G01N2570/00 , H01J49/00
摘要： The invention relates to a method for determining the presence of at least one distinct polypeptide in a biological sample comprising contacting the biological sample with a hydrolyzing agent, wherein the hydrolyzing agent is capable of hydrolyzing the distinct polypeptide in a sequence-specific manner such that at least one distinct peptide having a predetermined peptide measured accurate mass would result if the at least one distinct polypeptide were present in the biological sample, to obtain a hydrolyzed sample; bringing the hydrolyzed sample in contact with a substrate comprising at least one immobilized binding partner, wherein the at least one immobilized binding partner is capable of specifically binding the distinct peptide; removing the hydrolyzed sample from the substrate in a manner such that the distinct peptide would remain bound to the immobilized binding partner; contacting the substrate with an elution solution, wherein the distinct peptide would dissociate from the immobilized binding partner into the elution solution; subjecting a portion of the elution solution to liquid chromatography to segregate a plurality of molecules in the portion of the elution solution to obtain sorted molecules; determining the measured accurate mass of at least one sorted molecule present in the elution solution; and determining the presence of the at least one distinct polypeptide in the biological sample when a measured accurate mass of at least one molecule is substantially equal to the predetermined peptide measured accurate mass.
摘要翻译：本发明涉及一种用于确定生物样品中至少一种不同多肽的存在的方法，包括使生物样品与水解试剂接触，其中水解试剂能够以序列特异性方式水解不同的多肽，如果至少一种不同的多肽存在于生物样品中，则得到具有测定精确质量的预定肽的至少一种不同的肽，以获得水解样品; 使水解的样品与包含至少一个固定的结合配偶体的底物接触，其中至少一个固定的结合配偶体能够特异性结合不同的肽; 以使得不同的肽保持与固定的结合配偶体结合的方式从底物中除去水解的样品; 使所述底物与洗脱溶液接触，其中所述不同的肽将从固定的结合配偶体解离成洗脱溶液; 使洗脱溶液的一部分进行液相色谱分离洗脱溶液部分中的多个分子，得到分选的分子; 确定洗脱溶液中存在的至少一种分选分子的测量精确质量; 以及当所测量的至少一个分子的精确质量基本上等于所测量的精确质量的预定肽时，确定生物样品中至少一种不同多肽的存在。

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