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1. 发明授权

US09394571B2 Method for rapidly screening microbial hosts to identify certain strains with improved yield and/or quality in the expression of heterologous proteins 有权
标题翻译：用于快速筛选微生物宿主以鉴定具有提高异源蛋白质表达的产量和/或质量的某些菌株的方法
公开(公告)号：US09394571B2
公开(公告)日：2016-07-19
申请号：US12109554
申请日：2008-04-25
申请人： Thomas M. Ramseier , Russell J. Coleman , Jane C. Schneider , Charles D. Hershberger , Diane M. Retallack , Charles H. Squires
发明人： Thomas M. Ramseier , Russell J. Coleman , Jane C. Schneider , Charles D. Hershberger , Diane M. Retallack , Charles H. Squires
IPC分类号： G01N33/554 , C12N1/20 , C12N15/00 , C12P21/04 , C12P21/06 , C07H21/04 , C12Q1/68 , C12N15/78
CPC分类号： C12Q1/689 , C12N1/20 , C12N15/78
摘要： The present invention provides an array for rapidly identifying a host cell population capable of producing a heterologous protein with improved yield and/or quality. The array comprises one or more host cell populations that have been genetically modified to increase the expression of one or more target genes involved in protein production, decrease the expression of one or more target genes involved in protein degradation, or both. One or more of the strains in the array may express the heterologous protein of interest in a periplasm compartment or may secrete the heterologous protein extracellularly through an outer cell wall. The strain arrays are useful for screening for improved expression of any protein of interest including therapeutic proteins, hormones, growth factors, extracellular receptors or ligands, proteases, kinases, blood proteins, chemokines, cytokines, antibodies and the like.
摘要翻译：本发明提供了一种用于快速鉴定能够产生具有改善的产量和/或质量的异源蛋白质的宿主细胞群的阵列。该阵列包含已被遗传修饰的一个或多个宿主细胞群，以增加涉及蛋白质产生的一个或多个靶基因的表达，减少参与蛋白质降解的一个或多个靶基因的表达，或两者。阵列中的一个或多个菌株可以在周质隔室中表达感兴趣的异源蛋白质，或者通过外细胞壁在细胞外分泌异源蛋白质。菌株阵列可用于筛选任何目的蛋白质的表达，包括治疗性蛋白质，激素，生长因子，细胞外受体或配体，蛋白酶，激酶，血液蛋白，趋化因子，细胞因子，抗体等。

2. 发明授权

US09580719B2 Method for rapidly screening microbial hosts to identify certain strains with improved yield and/or quality in the expression of heterologous proteins 有权
标题翻译：用于快速筛选微生物宿主以鉴定具有提高异源蛋白质表达的产量和/或质量的某些菌株的方法
公开(公告)号：US09580719B2
公开(公告)日：2017-02-28
申请号：US12610207
申请日：2009-10-30
申请人： Diane M. Retallack , Charles H. Squires , Thomas M. Ramseier , Russell J. Coleman , Jane C. Schneider , Charles D. Hershberger
发明人： Diane M. Retallack , Charles H. Squires , Thomas M. Ramseier , Russell J. Coleman , Jane C. Schneider , Charles D. Hershberger
IPC分类号： C12N15/78
CPC分类号： C12N15/1037 , C12N15/78
摘要： The present invention provides an array for rapidly identifying a host cell population capable of producing a heterologous protein with improved yield and/or quality. The array comprises one or more host cell populations that have been genetically modified to increase the expression of one or more target genes involved in protein production, decrease the expression of one or more target genes involved in protein degradation, or both. One or more of the strains in the array may express the heterologous protein of interest in a periplasm compartment or may secrete the heterologous protein extracellularly through an outer cell wall. The strain arrays are useful for screening for improved expression of any protein of interest including therapeutic proteins, hormones, growth factors, extracellular receptors or ligands, proteases, kinases, blood proteins, chemokines, cytokines, antibodies and the like.
摘要翻译：本发明提供了一种用于快速鉴定能够产生具有改善的产量和/或质量的异源蛋白质的宿主细胞群的阵列。该阵列包含已被遗传修饰的一个或多个宿主细胞群，以增加参与蛋白质产生的一个或多个靶基因的表达，减少参与蛋白质降解的一个或多个靶基因的表达，或两者。阵列中的一个或多个菌株可以在周质隔室中表达感兴趣的异源蛋白质，或者通过外细胞壁在细胞外分泌异源蛋白质。菌株阵列可用于筛选任何目的蛋白质的表达，包括治疗性蛋白质，激素，生长因子，细胞外受体或配体，蛋白酶，激酶，血液蛋白，趋化因子，细胞因子，抗体等。

3. 发明申请

US20100137162A1 Method for Rapidly Screening Microbial Hosts to Identify Certain Strains with Improved Yield and/or Quality in the Expression of Heterologous Proteins 有权
标题翻译：快速筛选微生物宿主鉴定异源蛋白表达中产量和/或质量提高的某些菌株的方法
公开(公告)号：US20100137162A1
公开(公告)日：2010-06-03
申请号：US12610207
申请日：2009-10-30
申请人： Diane M. Retallack , Charles H. Squires , Thomas M. Ramseier , Russell J. Coleman , Jane C. Schneider , Charies D. Hershberger
发明人： Diane M. Retallack , Charles H. Squires , Thomas M. Ramseier , Russell J. Coleman , Jane C. Schneider , Charies D. Hershberger
IPC分类号： C40B30/10 , C40B50/06 , C40B40/02
CPC分类号： C12N15/1037 , C12N15/78
摘要： The present invention provides an array for rapidly identifying a host cell population capable of producing heterologous protein with improved yield and/or quality. The array comprises one or more host cell populations that have been genetically modified to increase the expression of one or more target genes involved in protein production, decrease the expression of one or more target genes involved in protein degradation, or both. One or more of the strains in the array may express the heterologous protein of interest in a periplasm compartment, or may secrete the heterologous protein extracellularly through an outer cell wall. The strain arrays are useful for screening for improved expression of any protein of interest, including therapeutic proteins, hormones, a growth factors, extracellular receptors or ligands, proteases, kinases, blood proteins, chemokines, cytokines, antibodies and the like.
摘要翻译：本发明提供了一种用于快速鉴定能够产生具有改善的产量和/或质量的异源蛋白质的宿主细胞群的阵列。该阵列包含已被遗传修饰的一个或多个宿主细胞群，以增加涉及蛋白质产生的一个或多个靶基因的表达，减少参与蛋白质降解的一个或多个靶基因的表达，或两者。阵列中的一个或多个菌株可以在周质隔室中表达感兴趣的异源蛋白质，或者通过外细胞壁在细胞外分泌异源蛋白质。菌株阵列可用于筛选任何目的蛋白质的表达，包括治疗性蛋白质，激素，生长因子，细胞外受体或配体，蛋白酶，激酶，血液蛋白，趋化因子，细胞因子，抗体等。

4. 发明授权

US07618799B2 Bacterial leader sequences for increased expression 有权
标题翻译：用于增加表达的细菌前导序列
公开(公告)号：US07618799B2
公开(公告)日：2009-11-17
申请号：US12022789
申请日：2008-01-30
申请人： Russell J. Coleman , Diane Retallack , Jane C. Schneider , Thomas M. Ramseier , Charles D. Hershberger , Stacey Lee , Sol M. Resnick
发明人： Russell J. Coleman , Diane Retallack , Jane C. Schneider , Thomas M. Ramseier , Charles D. Hershberger , Stacey Lee , Sol M. Resnick
IPC分类号： C12N9/00 , C12N15/00 , C12N1/04
CPC分类号： C12N15/625 , C07K2319/02 , C07K2319/036
摘要： Compositions and methods for improving expression and/or secretion of protein or polypeptide of interest in a host cell are provided. Compositions comprising a coding sequence for a bacterial secretion signal peptide are provided. The coding sequences can be used in vector constructs or expression systems for transformation and expression of a protein or polypeptide of interest in a host cell. The compositions of the invention are useful for increasing accumulation of properly processed proteins in the periplasmic space of a host cell, or for increasing secretion of properly processed proteins from the host cell. In particular, isolated secretion signal peptide-encoding nucleic acid molecules are provided. Additionally, amino acid sequences corresponding to the nucleic acid molecules are encompassed. In particular, the present invention provides for isolated nucleic acid molecules comprising nucleotide sequences encoding the amino acid sequences shown in SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24, and the nucleotide sequences set forth in SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, and 23, as well as variants and fragments thereof.
摘要翻译：提供用于改善宿主细胞中感兴趣的蛋白质或多肽的表达和/或分泌的组合物和方法。提供了包含细菌分泌信号肽的编码序列的组合物。编码序列可用于载体构建体或表达系统，用于在宿主细胞中转化和表达感兴趣的蛋白质或多肽。本发明的组合物可用于增加正确加工的蛋白质在宿主细胞的周质空间中的积累，或用于增加来自宿主细胞的适当加工的蛋白质的分泌。特别地，提供了分离信号肽编码核酸分子。另外，包含对应于核酸分子的氨基酸序列。特别地，本发明提供了包含编码SEQ ID NO：2,4,6,8,10,12,14,16,18,20,22和24所示氨基酸序列的核苷酸序列的分离的核酸分子。，以及SEQ ID NO：1,3,5,7,9,11,13,15,17,19,21和23所示的核苷酸序列，以及其变体和片段。

5. 发明申请

US20080269070A1 METHOD FOR RAPIDLY SCREENING MICROBIAL HOSTS TO IDENTIFY CERTAIN STRAINS WITH IMPROVED YIELD AND/OR QUALITY IN THE EXPRESSION OF HETEROLOGOUS PROTEINS 有权
标题翻译：用于快速筛选微生物宿主以鉴别异源蛋白质表达中具有改善的产量和/或质量的某些菌株的方法
公开(公告)号：US20080269070A1
公开(公告)日：2008-10-30
申请号：US12109554
申请日：2008-04-25
申请人： Thomas M. Ramseier , Russell J. Coleman , Jane C. Schneider , Charles D. Hershberger
发明人： Thomas M. Ramseier , Russell J. Coleman , Jane C. Schneider , Charles D. Hershberger
IPC分类号： C40B30/00 , C40B40/02
CPC分类号： C12Q1/689 , C12N1/20 , C12N15/78
摘要： The present invention provides an array for rapidly identifying a host cell population capable of producing heterologous protein with improved yield and/or quality. The array comprises one or more host cell populations that have been genetically modified to increase the expression of one or more target genes involved in protein production, decrease the expression of one or more target genes involved in protein degradation, or both. One or more of the strains in the array may express the heterologous protein of interest in a periplasm compartment, or may secrete the heterologous protein extracellularly through an outer cell wall. The strain arrays are useful for screening for improved expression of any protein of interest, including therapeutic proteins, hormones, a growth factors, extracellular receptors or ligands, proteases, kinases, blood proteins, chemokines, cytokines, antibodies and the like.
摘要翻译：本发明提供了一种用于快速鉴定能够产生具有改善的产量和/或质量的异源蛋白质的宿主细胞群的阵列。该阵列包含已被遗传修饰的一个或多个宿主细胞群，以增加涉及蛋白质产生的一个或多个靶基因的表达，减少参与蛋白质降解的一个或多个靶基因的表达，或两者。阵列中的一个或多个菌株可以在周质隔室中表达感兴趣的异源蛋白质，或者通过外细胞壁在细胞外分泌异源蛋白质。菌株阵列可用于筛选任何目的蛋白质的表达，包括治疗性蛋白质，激素，生长因子，细胞外受体或配体，蛋白酶，激酶，血液蛋白，趋化因子，细胞因子，抗体等。

6. 发明申请

US20080193974A1 BACTERIAL LEADER SEQUENCES FOR INCREASED EXPRESSION 有权
标题翻译：细菌引导序列增加表达
公开(公告)号：US20080193974A1
公开(公告)日：2008-08-14
申请号：US12022789
申请日：2008-01-30
申请人： Russell J. Coleman , Diane Retallack , Jane C. Schneider , Thomas M. Ramseier , Charles D. Hershberger , Stacey Lee , Sol M. Resnick
发明人： Russell J. Coleman , Diane Retallack , Jane C. Schneider , Thomas M. Ramseier , Charles D. Hershberger , Stacey Lee , Sol M. Resnick
IPC分类号： C12P21/04 , C12N15/11 , C12N15/00 , C12N1/20 , C07K14/00 , C12N9/90
CPC分类号： C12N15/625 , C07K2319/02 , C07K2319/036
摘要： Compositions and methods for improving expression and/or secretion of protein or polypeptide of interest in a host cell are provided. Compositions comprising a coding sequence for a bacterial secretion signal peptide are provided. The coding sequences can be used in vector constructs or expression systems for transformation and expression of a protein or polypeptide of interest in a host cell. The compositions of the invention are useful for increasing accumulation of properly processed proteins in the periplasmic space of a host cell, or for increasing secretion of properly processed proteins from the host cell. In particular, isolated secretion signal peptide-encoding nucleic acid molecules are provided. Additionally, amino acid sequences corresponding to the nucleic acid molecules are encompassed. In particular, the present invention provides for isolated nucleic acid molecules comprising nucleotide sequences encoding the amino acid sequences shown in SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24, and the nucleotide sequences set forth in SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, and 23, as well as variants and fragments thereof.
摘要翻译：提供用于改善宿主细胞中感兴趣的蛋白质或多肽的表达和/或分泌的组合物和方法。提供了包含细菌分泌信号肽的编码序列的组合物。编码序列可用于载体构建体或表达系统，用于在宿主细胞中转化和表达感兴趣的蛋白质或多肽。本发明的组合物可用于增加正确加工的蛋白质在宿主细胞的周质空间中的积累，或用于增加来自宿主细胞的适当加工的蛋白质的分泌。特别地，提供了分离信号肽编码核酸分子。另外，包含对应于核酸分子的氨基酸序列。特别地，本发明提供了包含编码SEQ ID NO：2,4,6,8,10,12,14,16,18,20,22和24所示氨基酸序列的核苷酸序列的分离的核酸分子。，以及SEQ ID NO：1,3,5,7,9,11,13,15,17,19,21和23所示的核苷酸序列，以及其变体和片段。

7. 发明授权

US07833752B2 Bacterial leader sequences for increased expression 有权
标题翻译：用于增加表达的细菌前导序列
公开(公告)号：US07833752B2
公开(公告)日：2010-11-16
申请号：US12604061
申请日：2009-10-22
申请人： Russell J. Coleman , Diane M. Retallack , Stacey L. Lee , Charles D. Hershberger
发明人： Russell J. Coleman , Diane M. Retallack , Stacey L. Lee , Charles D. Hershberger
IPC分类号： C12P21/06 , C12N1/20 , C12N15/00 , C07K1/00
CPC分类号： C12N15/625 , C07K2319/02 , C07K2319/036
摘要： Compositions and methods for improving expression and/or secretion of a polypeptide of interest in a host cell are provided. Compositions including a coding sequence for a bacterial secretion signal peptide are provided. The compositions of the invention are useful for increasing accumulation of properly processed proteins in the periplasmic space of a host cell, or for increasing secretion of properly processed proteins. In particular, isolated secretion signal peptide-encoding nucleic acid molecules are provided. Additionally, amino acid sequences corresponding to the nucleic acid molecules are encompassed. The present invention provides for isolated nucleic acid molecules including nucleotide sequences encoding the amino acid sequences shown in SEQ ID NO:2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24, and the nucleotide sequences set forth in SEQ ID NO:1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, and 23, as well as variants and fragments thereof.
摘要翻译：提供用于改善宿主细胞中感兴趣的多肽的表达和/或分泌的组合物和方法。提供了包括细菌分泌信号肽的编码序列的组合物。本发明的组合物可用于增加适当加工的蛋白质在宿主细胞的周质空间中的积累，或用于增加适当加工的蛋白质的分泌。特别地，提供了分离信号肽编码核酸分子。另外，包含对应于核酸分子的氨基酸序列。本发明提供了分离的核酸分子，包括编码SEQ ID NO：2,4,6,8,10,12,14,16,18,20,22和24所示的氨基酸序列的核苷酸序列， SEQ ID NO：1,3,5,7,9,11,13,15,17,19,21和23所示的核苷酸序列，以及其变体和片段。

8. 发明申请

US20090062143A1 TRANSLATION INITIATION REGION SEQUENCES FOR OPTIMAL EXPRESSION OF HETEROLOGOUS PROTEINS 审中-公开
标题翻译：翻译启动区序列用于优化表达异源蛋白
公开(公告)号：US20090062143A1
公开(公告)日：2009-03-05
申请号：US12185726
申请日：2008-08-04
申请人： Thomas M. Ramseier , Russell J. Coleman , Jane C. Schneider
发明人： Thomas M. Ramseier , Russell J. Coleman , Jane C. Schneider
IPC分类号： C40B30/06 , C07H21/00 , C12N15/63 , C12N1/00 , C40B40/06
CPC分类号： C12N15/67 , C12N15/1051
摘要： The present invention provides methods and compositions for producing heterologous protein with improved yield and/or quality. A library of randomized ribosomal binding site sequences is provided for the identification of a translation initiation region sequence optimal for expression of the heterologous protein. Also provided are novel ribosomal binding site sequences, and vectors and host cells having those sequences. The library of randomized sequences is useful for screening for improved expression of any protein of interest, including therapeutic proteins, hormones, a growth factors, extracellular receptors or ligands, proteases, kinases, blood proteins, chemokines, cytokines, antibodies and the like.
摘要翻译：本发明提供用于产生具有改善的产量和/或质量的异源蛋白质的方法和组合物。提供随机核糖体结合位点序列的文库用于鉴定用于表达异源蛋白质的最佳翻译起始区序列。还提供了新的核糖体结合位点序列，以及具有那些序列的载体和宿主细胞。随机序列文库可用于筛选任何目标蛋白的表达，包括治疗性蛋白质，激素，生长因子，细胞外受体或配体，蛋白酶，激酶，血液蛋白，趋化因子，细胞因子，抗体等。

9. 发明申请

US20110020868A1 BACTERIAL LEADER SEQUENCES FOR INCREASED EXPRESSION 审中-公开
标题翻译：细菌引导序列增加表达
公开(公告)号：US20110020868A1
公开(公告)日：2011-01-27
申请号：US12884095
申请日：2010-09-16
申请人： Russell J. Coleman , Diane Retallack , Stacey L. Lee , Charles D. Hershberger
发明人： Russell J. Coleman , Diane Retallack , Stacey L. Lee , Charles D. Hershberger
IPC分类号： C12P21/00 , C07H21/04 , C12N15/63 , C12N1/21 , C07K2/00 , C12N9/90 , C07K14/00
CPC分类号： C12N15/625 , C07K2319/02 , C07K2319/036
摘要： Compositions and methods for improving expression and/or secretion of a polypeptide of interest in a host cell are provided. Compositions including a coding sequence for a bacterial secretion signal peptide are provided. The compositions of the invention are useful for increasing accumulation of properly processed proteins in the periplasmic space of a host cell, or for increasing secretion of properly processed proteins. In particular, isolated secretion signal peptide-encoding nucleic acid molecules are provided. Additionally, amino acid sequences corresponding to the nucleic acid molecules are encompassed. The present invention provides for isolated nucleic acid molecules including nucleotide sequences encoding the amino acid sequences shown in SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24, and the nucleotide sequences set forth in SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, and 23, as well as variants and fragments thereof.
摘要翻译：提供用于改善宿主细胞中感兴趣的多肽的表达和/或分泌的组合物和方法。提供了包括细菌分泌信号肽的编码序列的组合物。本发明的组合物可用于增加适当加工的蛋白质在宿主细胞的周质空间中的积累，或用于增加适当加工的蛋白质的分泌。特别地，提供了分离信号肽编码核酸分子。另外，包含对应于核酸分子的氨基酸序列。本发明提供了分离的核酸分子，包括编码SEQ ID NO：2,4,6,8,10,12,14,16,18,20,22和24所示的氨基酸序列的核苷酸序列， SEQ ID NO：1,3,5,7,9,11,13,15,17,19,21和23所示的核苷酸序列，以及其变体和片段。

10. 发明申请

US20100048864A1 BACTERIAL LEADER SEQUENCES FOR INCREASED EXPRESSION 有权
标题翻译：细菌引导序列增加表达
公开(公告)号：US20100048864A1
公开(公告)日：2010-02-25
申请号：US12604061
申请日：2009-10-22
申请人： Russell J. Coleman , Diane Retallack , Charles D. Hershberger , Stacey Lee
发明人： Russell J. Coleman , Diane Retallack , Charles D. Hershberger , Stacey Lee
IPC分类号： C07K14/21 , C12P21/06 , C12N1/21 , C12N15/63 , C07H21/04
CPC分类号： C12N15/625 , C07K2319/02 , C07K2319/036
摘要： Compositions and methods for improving expression and/or secretion of a polypeptide of interest in a host cell are provided. Compositions including a coding sequence for a bacterial secretion signal peptide are provided. The compositions of the invention are useful for increasing accumulation of properly processed proteins in the periplasmic space of a host cell, or for increasing secretion of properly processed proteins. In particular, isolated secretion signal peptide-encoding nucleic acid molecules are provided. Additionally, amino acid sequences corresponding to the nucleic acid molecules are encompassed. The present invention provides for isolated nucleic acid molecules including nucleotide sequences encoding the amino acid sequences shown in SEQ ID NO:2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24, and the nucleotide sequences set forth in SEQ ID NO:1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, and 23, as well as variants and fragments thereof.
摘要翻译：提供用于改善宿主细胞中感兴趣的多肽的表达和/或分泌的组合物和方法。提供了包括细菌分泌信号肽的编码序列的组合物。本发明的组合物可用于增加适当加工的蛋白质在宿主细胞的周质空间中的积累，或用于增加适当加工的蛋白质的分泌。特别地，提供了分离信号肽编码核酸分子。另外，包含对应于核酸分子的氨基酸序列。本发明提供了分离的核酸分子，包括编码SEQ ID NO：2,4,6,8,10,12,14,16,18,20,22和24所示的氨基酸序列的核苷酸序列， SEQ ID NO：1,3,5,7,9,11,13,15,17,19,21和23所示的核苷酸序列，以及其变体和片段。

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