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1. 发明申请

US20080131427A1 Whole Genome Evolution Technology Applied To Improve Protein And Antibody Yields By Cells 审中-公开
标题翻译：全基因组进化技术应用于提高细胞的蛋白质和抗体产量
公开(公告)号：US20080131427A1
公开(公告)日：2008-06-05
申请号：US11735707
申请日：2007-04-16
申请人： J. Bradford Kline , Qimin Chao , Philip M. Sass , Luigi Grasso , Nicholas C. Nicolaides
发明人： J. Bradford Kline , Qimin Chao , Philip M. Sass , Luigi Grasso , Nicholas C. Nicolaides
IPC分类号： A61K39/395 , C12N5/06
CPC分类号： C12N15/01 , C12N15/1024 , C12N15/1079
摘要： Whole Genome Evolution Technology can be considered a broad tool for supporting the needs for scaleable manufacturing of therapeutic antibodies. Its random nature and in vivo mode of action separate this process from other complementary technologies, thus providing alternative solutions to improve a host cell's manufacturing performance. The speed with which a pre-existing production strain can be optimized makes this process suitable for satisfying the current need for rapid cell line optimization to produce faster growing cells exhibiting high titers of antibody at the preclinical, clinical or commercialization stage.
摘要翻译：全基因组进化技术可以被认为是支持可扩展制造治疗性抗体需求的广泛工具。其随机性质和体内作用模式将该过程与其他互补技术分开，从而提供替代解决方案来改善宿主细胞的制造性能。可以优化预先存在的生产菌株的速度使得该方法适合于满足目前对快速细胞系优化的需要，以在临床前，临床或商业化阶段产生更高生长细胞，其表现出高滴度抗体。

2. 发明授权

US07638334B2 Method for generating engineered cells by homologously recombining segments having increased degeneracy 有权
标题翻译：通过同源重组具有增加的简并性的片段产生工程细胞的方法
公开(公告)号：US07638334B2
公开(公告)日：2009-12-29
申请号：US10348074
申请日：2003-01-17
申请人： Nicholas C. Nicolaides , J. Bradford Kline , Luigi Grasso , Philip M. Sass
发明人： Nicholas C. Nicolaides , J. Bradford Kline , Luigi Grasso , Philip M. Sass
IPC分类号： C12N15/87 , C12N1/12 , C12N15/74 , A01N63/00 , A01N65/00 , A01N63/04 , A61K48/00 , C12Q1/68 , A01N43/04 , A61K31/70
CPC分类号： C12N15/905 , C12N15/102 , C12N15/902 , C12N15/907
摘要： Inhibitors of mismatch repair can be used to generate hypermutable cells and organisms. By inhibiting this process in cells, new cell lines and varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of homologous recombination. These methods are useful for generating targeted loci that can alter the expression profiles of target genes as well as tag exons of a gene with a reporter marker to facilitate the monitoring of a given gene product when the host is grown under different conditions or exposed to biological and chemical entities.
摘要翻译：不匹配修复的抑制剂可用于产生超可变细胞和生物体。通过在细胞中抑制该过程，可以比通过依赖于同源重组的天然速率更有效地制备具有新颖和有用性质的新细胞系和品种。这些方法可用于产生靶基因座，其可以改变目标基因的表达谱以及用报道标记的基因的标签外显子，以便当宿主在不同条件下生长或暴露于生物时使其监测给定的基因产物和化学实体。

3. 发明申请

US20090155797A1 Methods For Generating Enhanced Antibody-Producing Cell Lines With Improved Growth Characteristics 审中-公开
标题翻译：用于产生具有改善生长特性的增强型抗体生产细胞系的方法
公开(公告)号：US20090155797A1
公开(公告)日：2009-06-18
申请号：US12277743
申请日：2008-11-25
申请人： Luigi Grasso , J. Bradford Kline , Nicholas C. Nicolaides , Philip M. Sass
发明人： Luigi Grasso , J. Bradford Kline , Nicholas C. Nicolaides , Philip M. Sass
IPC分类号： C12Q1/68 , C12N5/10 , C12N5/00
CPC分类号： C12N15/1024 , C07K16/00 , C12N15/1034
摘要： The use of mismatch repair (MMR) defective antibody producer cells offers a method to generate subclone variants with elevated protein production such as antibodies. Using MMR defective cells and animals, new cell lines and animal varieties with novel and useful properties such as enhanced protein production can be generated more efficiently than by relying on the natural rate of mutation. These methods are useful for generating genetic diversity within host cells to alter endogenous genes that can yield increased titer levels of protein production. By employing this method, two genes were discovered whose suppressed expression is associated with enhanced antibody production. Suppressed expression of these genes by a variety of methods leads to increased antibody production for manufacturing as well as strategies for modulating antibody production in immunological disorders. Moreover, the suppression of these two genes in host cells can be useful for generating universal high titer protein production lines.
摘要翻译：使用错配修复（MMR）缺陷抗体生产细胞提供了产生具有升高的蛋白质产生的亚克隆变体的方法，例如抗体。使用MMR缺陷细胞和动物，可以比通过依赖于自然的突变率更有效地产生具有新颖有用性质的新细胞系和动物品种，例如增强的蛋白质产生。这些方法可用于在宿主细胞内产生遗传多样性以改变可产生增加的蛋白质产生效价水平的内源基因。通过采用这种方法，发现了两个基因，其抑制表达与抗体产生增强有关。通过多种方法抑制这些基因的表达导致增加的制造抗体产生以及用于调节免疫疾病中的抗体产生的策略。此外，在宿主细胞中抑制这两种基因可用于产生通用高滴度蛋白质生产线。

4. 发明授权

US07741450B2 Antibodies to GM-CSF 有权
标题翻译： GM-CSF抗体
公开(公告)号：US07741450B2
公开(公告)日：2010-06-22
申请号：US11672902
申请日：2007-02-08
申请人： Philip M. Sass , Nicholas C. Nicolaides , Luigi Grasso , Jian Li , Qimin Chao , Eric Routhier , Wolfgang Ebel
发明人： Philip M. Sass , Nicholas C. Nicolaides , Luigi Grasso , Jian Li , Qimin Chao , Eric Routhier , Wolfgang Ebel
IPC分类号： C07K16/24 , C12N5/12
CPC分类号： C07K16/243 , A61K39/395 , A61K39/3955 , A61K2039/505 , C07K16/00 , C07K16/22 , C07K2317/21 , C07K2317/33 , C07K2317/34 , C07K2317/56 , C07K2317/565 , C07K2317/73 , C07K2317/76 , C07K2317/92 , C12N15/09 , C12N15/63
摘要： Hybridoma lines that secrete human monoclonal antibodies with high binding specificity and biological activity, particularly neutralizing activity against granulocyte-macrophage colony stimulating factor, and methods of generating the hybridoma lines are provided. Target antigens and epitopes are also provided. The antibodies may be used in therapeutic methods, for example in the treatment of cancer, infectious disease, or autoimmune disease.
摘要翻译：提供了分泌具有高结合特异性和生物活性的人单克隆抗体的杂交瘤系，特别是针对粒细胞 - 巨噬细胞集落刺激因子的中和活性，以及产生杂交瘤系的方法。还提供靶抗原和表位。抗体可用于治疗方法，例如用于治疗癌症，感染性疾病或自身免疫性疾病。

5. 发明申请

US20140086928A1 Antigenic GM-CSF Peptides and Antibodies to GM-CSF 有权
标题翻译：抗原GM-CSF肽和GM-CSF抗体
公开(公告)号：US20140086928A1
公开(公告)日：2014-03-27
申请号：US14091028
申请日：2013-11-26
申请人： Philip M. Sass , Nicholas C. Nicolaides , Luigi Grasso , Jian Li , Qimin Chao , Eric Routhier , Wolfgang Ebel
发明人： Philip M. Sass , Nicholas C. Nicolaides , Luigi Grasso , Jian Li , Qimin Chao , Eric Routhier , Wolfgang Ebel
IPC分类号： C07K16/24
CPC分类号： C07K16/243 , A61K39/395 , A61K39/3955 , A61K2039/505 , C07K16/00 , C07K16/22 , C07K2317/21 , C07K2317/33 , C07K2317/34 , C07K2317/56 , C07K2317/565 , C07K2317/73 , C07K2317/76 , C07K2317/92 , C12N15/09 , C12N15/63
摘要： Hybridoma lines that secrete human monoclonal antibodies with high binding specificity and biological activity, particularly neutralizing activity against granulocyte-macrophage colony stimulating factor, and methods of generating the hybridoma lines are provided. Target antigens and epitopes are also provided. The antibodies may be used in therapeutic methods, for example in the treatment of cancer, infectious disease, or autoimmune disease.
摘要翻译：提供了分泌具有高结合特异性和生物活性的人单克隆抗体的杂交瘤系，特别是针对粒细胞 - 巨噬细胞集落刺激因子的中和活性，以及产生杂交瘤系的方法。还提供靶抗原和表位。抗体可用于治疗方法，例如用于治疗癌症，感染性疾病或自身免疫性疾病。

6. 发明授权

US08318168B2 Antigenic GM-CSF peptides and antibodies to GM-CSF 有权
标题翻译：抗原GM-CSF肽和GM-CSF抗体
公开(公告)号：US08318168B2
公开(公告)日：2012-11-27
申请号：US12761464
申请日：2010-04-16
申请人： Philip M. Sass , Nicholas C. Nicolaides , Luigi Grasso , Jian Li , Qimin Chao , Eric Routhier , Wolfgang Ebel
发明人： Philip M. Sass , Nicholas C. Nicolaides , Luigi Grasso , Jian Li , Qimin Chao , Eric Routhier , Wolfgang Ebel
IPC分类号： A61K39/395 , C07K16/22 , C12P21/08
CPC分类号： C07K16/243 , A61K39/395 , A61K39/3955 , A61K2039/505 , C07K16/00 , C07K16/22 , C07K2317/21 , C07K2317/33 , C07K2317/34 , C07K2317/56 , C07K2317/565 , C07K2317/73 , C07K2317/76 , C07K2317/92 , C12N15/09 , C12N15/63
摘要： Hybridoma lines that secrete human monoclonal antibodies with high binding specificity and biological activity, particularly neutralizing activity against granulocyte-macrophage colony stimulating factor, and methods of generating the hybridoma lines are provided. Target antigens and epitopes are also provided. The antibodies may be used in therapeutic methods, for example in the treatment of cancer, infectious disease, or autoimmune disease.
摘要翻译：提供了分泌具有高结合特异性和生物活性的人单克隆抗体的杂交瘤系，特别是针对粒细胞 - 巨噬细胞集落刺激因子的中和活性，以及产生杂交瘤系的方法。还提供靶抗原和表位。抗体可用于治疗方法，例如用于治疗癌症，感染性疾病或自身免疫性疾病。

7. 发明授权

US08623364B2 Antigenic GM-CSF peptides and antibodies to GM-CSF 有权
标题翻译：抗原GM-CSF肽和GM-CSF抗体
公开(公告)号：US08623364B2
公开(公告)日：2014-01-07
申请号：US13659165
申请日：2012-10-24
申请人： Philip M. Sass , Nicholas C. Nicolaides , Luigi Grasso , Jian Li , Qimin Chao , Eric Routhier , Wolfgang Ebel
发明人： Philip M. Sass , Nicholas C. Nicolaides , Luigi Grasso , Jian Li , Qimin Chao , Eric Routhier , Wolfgang Ebel
IPC分类号： A61K39/395 , C07K16/00 , C07K16/22 , C12P21/08
CPC分类号： C07K16/243 , A61K39/395 , A61K39/3955 , A61K2039/505 , C07K16/00 , C07K16/22 , C07K2317/21 , C07K2317/33 , C07K2317/34 , C07K2317/56 , C07K2317/565 , C07K2317/73 , C07K2317/76 , C07K2317/92 , C12N15/09 , C12N15/63
摘要： Hybridoma lines that secrete human monoclonal antibodies with high binding specificity and biological activity, particularly neutralizing activity against granulocyte-macrophage colony stimulating factor, and methods of generating the hybridoma lines are provided. Target antigens and epitopes are also provided. The antibodies may be used in therapeutic methods, for example in the treatment of cancer, infectious disease, or autoimmune disease.
摘要翻译：提供了分泌具有高结合特异性和生物活性的人单克隆抗体的杂交瘤系，特别是针对粒细胞 - 巨噬细胞集落刺激因子的中和活性，以及产生杂交瘤系的方法。还提供靶抗原和表位。抗体可用于治疗方法，例如用于治疗癌症，感染性疾病或自身免疫性疾病。

8. 发明申请

US20130058945A1 Antigenic GM-CSF Peptides and Antibodies to GM-CSF 有权
标题翻译：抗原GM-CSF肽和GM-CSF抗体
公开(公告)号：US20130058945A1
公开(公告)日：2013-03-07
申请号：US13659165
申请日：2012-10-24
申请人： Philip M. Sass , Nicholas C. Nicolaides , Luigi Grasso , Jian Li , Qimin Chao , Eric Routhier , Wolfgang Ebel
发明人： Philip M. Sass , Nicholas C. Nicolaides , Luigi Grasso , Jian Li , Qimin Chao , Eric Routhier , Wolfgang Ebel
IPC分类号： A61K39/395 , C07K16/24 , C12N5/10 , C12N15/13 , C12N15/85
CPC分类号： C07K16/243 , A61K39/395 , A61K39/3955 , A61K2039/505 , C07K16/00 , C07K16/22 , C07K2317/21 , C07K2317/33 , C07K2317/34 , C07K2317/56 , C07K2317/565 , C07K2317/73 , C07K2317/76 , C07K2317/92 , C12N15/09 , C12N15/63
摘要： Hybridoma lines that secrete human monoclonal antibodies with high binding specificity and biological activity, particularly neutralizing activity against granulocyte-macrophage colony stimulating factor, and methods of generating the hybridoma lines are provided. Target antigens and epitopes are also provided. The antibodies may be used in therapeutic methods, for example in the treatment of cancer, infectious disease, or autoimmune disease.
摘要翻译：提供了分泌具有高结合特异性和生物活性的人单克隆抗体的杂交瘤系，特别是针对粒细胞 - 巨噬细胞集落刺激因子的中和活性，以及产生杂交瘤系的方法。还提供靶抗原和表位。抗体可用于治疗方法，例如用于治疗癌症，感染性疾病或自身免疫性疾病。

9. 发明申请

US20100272730A1 Antigenic GM-CSF Peptides And Antibodies To GM-CSF 有权
标题翻译：抗原GM-CSF肽和抗体对GM-CSF
公开(公告)号：US20100272730A1
公开(公告)日：2010-10-28
申请号：US12761464
申请日：2010-04-16
申请人： Philip M. Sass , Nicholas C. Nicolaides , Luigi Grasso , Jian Li , Qimin Chao , Eric Routhier , Wolfgang Ebel
发明人： Philip M. Sass , Nicholas C. Nicolaides , Luigi Grasso , Jian Li , Qimin Chao , Eric Routhier , Wolfgang Ebel
IPC分类号： A61K39/395 , C07K16/24 , C07H21/04 , C12N15/63 , C12N5/12 , A61P29/00 , A61P35/00 , A61P35/02
CPC分类号： C07K16/243 , A61K39/395 , A61K39/3955 , A61K2039/505 , C07K16/00 , C07K16/22 , C07K2317/21 , C07K2317/33 , C07K2317/34 , C07K2317/56 , C07K2317/565 , C07K2317/73 , C07K2317/76 , C07K2317/92 , C12N15/09 , C12N15/63
摘要： Hybridoma lines that secrete human monoclonal antibodies with high binding specificity and biological activity, particularly neutralizing activity against granulocyte-macrophage colony stimulating factor, and methods of generating the hybridoma lines are provided. Target antigens and epitopes are also provided. The antibodies may be used in therapeutic methods, for example in the treatment of cancer, infectious disease, or autoimmune disease.
摘要翻译：提供了分泌具有高结合特异性和生物活性的人单克隆抗体的杂交瘤系，特别是针对粒细胞 - 巨噬细胞集落刺激因子的中和活性，以及产生杂交瘤系的方法。还提供靶抗原和表位。抗体可用于治疗方法，例如用于治疗癌症，感染性疾病或自身免疫性疾病。

10. 发明申请

US20080292641A1 Antigenic GM-CSF peptides and antibodies to GM-CSF 有权
标题翻译：抗原GM-CSF肽和GM-CSF抗体
公开(公告)号：US20080292641A1
公开(公告)日：2008-11-27
申请号：US11672902
申请日：2007-02-08
申请人： Philip M. Sass , Nicholas C. Nicolaides , Luigi Grasso , Jian Li , Qimin Chao , Eric Routhier , Wolfgang Ebel
发明人： Philip M. Sass , Nicholas C. Nicolaides , Luigi Grasso , Jian Li , Qimin Chao , Eric Routhier , Wolfgang Ebel
IPC分类号： A61K39/395 , C07K16/18 , C12N15/11 , C12N15/00 , C12N5/06 , C12Q1/02 , C12P21/04 , C07K7/00 , A61P37/00
CPC分类号： C07K16/243 , A61K39/395 , A61K39/3955 , A61K2039/505 , C07K16/00 , C07K16/22 , C07K2317/21 , C07K2317/33 , C07K2317/34 , C07K2317/56 , C07K2317/565 , C07K2317/73 , C07K2317/76 , C07K2317/92 , C12N15/09 , C12N15/63
摘要： Hybridoma lines that secrete human monoclonal antibodies with high binding specificity and biological activity, particularly neutralizing activity against granulocyte-macrophage colony stimulating factor, and methods of generating the hybridoma lines are provided. Target antigens and epitopes are also provided. The antibodies may be used in therapeutic methods, for example in the treatment of cancer, infectious disease, or autoimmune disease.
摘要翻译：提供了分泌具有高结合特异性和生物活性的人单克隆抗体的杂交瘤系，特别是针对粒细胞 - 巨噬细胞集落刺激因子的中和活性，以及产生杂交瘤系的方法。还提供靶抗原和表位。抗体可用于治疗方法，例如用于治疗癌症，感染性疾病或自身免疫性疾病。

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