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41.发明授权Methods of generating high-production of antibodies from hybridomas created by in vitro immunization 有权从通过体外免疫产生的杂交瘤产生高产量抗体的方法公开(公告)号：US08445229B2
公开(公告)日：2013-05-21
申请号：US12786530
申请日：2010-05-25
CPC分类号： C12N15/01 , C07K16/00 , C07K16/1282 , C07K16/243 , C07K16/2863 , C07K16/30 , C07K2317/21 , C07K2317/73 , C12N15/1024
摘要： The invention provides methods for generating high titers of high-affinity antibodies from hybridoma cells produced by fusing myeloma cells with in vitro immunized donor cells. The hybridoma cells or mammalian expression cells with cloned antibody genes from the hybridomas producing the high-affinity antibodies may be mismatch repair defective due to defects of endogenous mismatch repair subunits of through expression of a dominant negative allele of a mismatch repair gene which allows the hybridoma cell to be hypermutable, may be rendered hypermutable by chemical means, or may be naturally mismatch repair deficient. High-affinity antibodies and high titer producer cells producing antibodies may be prepared by the methods of the invention.
摘要翻译： 本发明提供了通过将骨髓瘤细胞与体外免疫的供体细胞融合而产生的杂交瘤细胞产生高亲和力抗体的高滴度的方法。 具有来自产生高亲和力抗体的杂交瘤的克隆抗体基因的杂交瘤细胞或哺乳动物表达细胞可能是错配修复缺陷，这是由于通过表达不匹配修复基因的显性负等位基因的内源性错配修复亚基的缺陷而允许杂交瘤 细胞可变性，可以通过化学方式使其变得过度，或者可能是天然错配修复缺陷。 可以通过本发明的方法制备产生抗体的高亲和力抗体和高滴度产生细胞。
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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。
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43.发明授权Antibodies with immune effector activity and that internalize in folate receptor alpha-positive cells 有权具有免疫效应物活性的抗体并且内化于叶酸受体α阳性细胞中公开(公告)号：US08124083B2
公开(公告)日：2012-02-28
申请号：US12503983
申请日：2009-07-16
IPC分类号： A61K39/395 , A61P35/00
CPC分类号： C07K16/30 , A61K31/704 , A61K31/7068 , A61K39/39558 , A61K47/6825 , A61K47/6851 , A61K47/6869 , A61K47/6897 , B82Y5/00 , C07K16/22 , C07K16/28 , C07K16/3069 , C07K2317/21 , C07K2317/24 , C07K2317/732 , C07K2317/76 , C07K2317/77
摘要： This invention relates to the use of monoclonal and polyclonal antibodies that specifically bind to and have the ability in the alternative to become internalized by cells expressing folate receptor alpha (FRA) and to induce an immune effector activity such as antibody-dependent cellular cytotoxicity. The antibodies are useful in specific delivery of pharmacologic agents to FRA-expressing cells as well as in eliciting an immune-effector activity particularly on tumor cells and precursors. The invention is also related to nucleotides encoding the antibodies of the invention, cells expressing the antibodies; methods of detecting cancer cells; and methods of treating cancer using the antibodies.
摘要翻译： 本发明涉及单克隆抗体和多克隆抗体的用途，其特异性结合并具有替代性的能力，其被表达叶酸受体α（FRA）的细胞内化，并诱导免疫效应物活性如抗体依赖性细胞毒性。 所述抗体可用于特异性递送表达FRA的细胞的药理学物质，以及引发特异性的肿瘤细胞和前体的免疫效应物活性。 本发明还涉及编码本发明抗体的核苷酸，表达抗体的细胞; 检测癌细胞的方法; 以及使用抗体治疗癌症的方法。
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44.发明授权Antibodies and methods for generating genetically altered antibodies with enhanced effector function 有权用于产生具有增强的效应子功能的遗传改变的抗体的抗体和方法公开(公告)号：US07807416B2
公开(公告)日：2010-10-05
申请号：US12251889
申请日：2008-10-15
IPC分类号： C12P21/08
CPC分类号： C12N15/1024 , C07K16/00 , C07K16/4291 , C07K2317/732 , C07K2317/92
摘要： Dominant negative alleles of human mismatch repair genes can be used to generate hypermutable cells and organisms. By introducing these genes into cells and transgenic animals, new cell lines and animal varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of mutation. These methods are useful for generating genetic diversity within immunoglobulin genes directed against an antigen of interest to produce altered antibodies with enhanced biochemical activity. Moreover, these methods are useful for generating antibody-producing cells with increased level of antibody production. The invention also provides methods for increasing the effector function of monoclonal antibodies and monoclonal antibodies with increased effector function.
摘要翻译： 人类错配修复基因的主要阴性等位基因可用于产生超可变细胞和生物体。 通过将这些基因引入细胞和转基因动物，可以比通过依赖于突变的自然速率更有效地制备具有新颖和有用性质的新细胞系和动物品种。 这些方法可用于在针对感兴趣的抗原的免疫球蛋白基因内产生遗传多样性，以产生具有增强的生化活性的改变的抗体。 此外，这些方法可用于产生具有增加的抗体产生水平的产生抗体的细胞。 本发明还提供了增加效应子功能增强的单克隆抗体和单克隆抗体的效应子功能的方法。
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公开(公告)号：US07759121B2
公开(公告)日：2010-07-20
申请号：US11930400
申请日：2007-10-31
IPC分类号： C12N15/01
CPC分类号： C12N15/81
摘要： Yeast cells are mutagenized to obtain desirable mutants. Mutagenesis is mediated by a defective mismatch repair system which can be enhanced using conventional exogenously applied mutagens. Yeast cells with the defective mismatch repair system are hypermutable, but after selection of desired mutant yeast strains, they can be rendered genetically stable by restoring the mismatch repair system to proper functionality.
摘要翻译： 酵母细胞被诱变以获得所需的突变体。 诱变由缺陷错配修复系统介导，可以使用常规的外源应用诱变剂进行增强。 具有缺陷错配修复系统的酵母细胞是可超过可变的，但是在选择所需的突变酵母菌株之后，可以通过将错配修复系统恢复到适当的功能来使它们变得遗传稳定。
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46.发明授权Methods of generating high-production of antibodies from hybridomas created by in vitro immunization 有权从通过体外免疫产生的杂交瘤产生高产量抗体的方法公开(公告)号：US07754450B2
公开(公告)日：2010-07-13
申请号：US10714228
申请日：2003-11-14
IPC分类号： C12P21/08
CPC分类号： C12N15/01 , C07K16/00 , C07K16/1282 , C07K16/243 , C07K16/2863 , C07K16/30 , C07K2317/21 , C07K2317/73 , C12N15/1024
摘要： The invention provides methods for generating high titers of high-affinity antibodies from hybridoma cells produced by fusing myeloma cells with in vitro immunized donor cells. The hybridoma cells or mammalian expression cells with cloned antibody genes from the hybridomas producing the high-affinity antibodies may be mismatch repair defective due to defects of endogenous mismatch repair subunits of through expression of a dominant negative allele of a mismatch repair gene which allows the hybridoma cell to be hypermutable, may be rendered hypermutable by chemical means, or may be naturally mismatch repair deficient. High-affinity antibodies and high titer producer cells producing antibodies may be prepared by the methods of the invention.
摘要翻译： 本发明提供了通过将骨髓瘤细胞与体外免疫的供体细胞融合而产生的杂交瘤细胞产生高亲和力抗体的高滴度的方法。 具有来自产生高亲和力抗体的杂交瘤的克隆抗体基因的杂交瘤细胞或哺乳动物表达细胞可能是错配修复缺陷，这是由于通过表达不匹配修复基因的显性负等位基因的内源性错配修复亚基的缺陷而允许杂交瘤 细胞可变性，可以通过化学方式使其变得过度，或者可能是天然错配修复缺陷。 可以通过本发明的方法制备产生抗体的高亲和力抗体和高滴度产生细胞。
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公开(公告)号：US07704689B2
公开(公告)日：2010-04-27
申请号：US11128420
申请日：2005-05-13
IPC分类号： C12Q1/68
CPC分类号： C12N15/1024 , C07K14/415 , C12N15/8216 , C12N15/8241
摘要： Blockade of mismatch repair in a plant can lead to hypermutation and a new genotype and/or phenotype. One approach used to generate hypermutable plants is through the expression of dominant negative alleles of mismatch repair genes in transgenic plants or derived cells. By introducing these genes into cells and transgenic plants, new cell lines and plant varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of mutation. Moreover, methods to inhibit the expression and activity of endogenous plant MMR genes and their encoded products are also useful to generate hypermutable plants.
摘要翻译： 植物中错配修复的阻断可导致超突变和新的基因型和/或表型。 用于产生超可变植物的一种方法是通过在转基因植物或衍生细胞中表达错配修复基因的显性负等位基因。 通过将这些基因引入细胞和转基因植物，可以比通过依赖于突变的自然速率更有效地制备具有新颖和有用性质的新细胞系和植物品种。 此外，抑制内源植物MMR基因及其编码产物的表达和活性的方法也可用于产生高可变性植物。
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48.发明授权Genetically altered antibody-producing cell lines with improved antibody characteristics 失效遗传改变的产生抗体的细胞系具有改善的抗体特征公开(公告)号：US07604994B2
公开(公告)日：2009-10-20
申请号：US10933034
申请日：2004-09-02
IPC分类号： C12N15/00
CPC分类号： C12N15/1024 , C07H21/04 , C07K16/00 , C07K16/4291 , C12N5/12 , C12N2501/052 , C12N2501/15 , C12N2501/23 , C12N2501/52 , C12N2510/02
摘要： Dominant negative alleles of human mismatch repair genes can be used to generate hypermutable cells and organisms. Cells may be selected for expression of activation-induced cytidine deaminase (AID), stimulated to produce AID, or manipulated to express AID for further enhancement of hypermutability. These methods are useful for generating genetic diversity within immunoglobulin genes directed against an antigen of interest to produce altered antibodies with enhanced biochemical activity. Moreover, these methods are useful for generating antibody-producing cells with increased level of antibody production.
摘要翻译： 人类错配修复基因的主要阴性等位基因可用于产生超可变细胞和生物体。 可以选择细胞用于表达活化诱导的胞苷脱氨酶（AID），刺激产生AID，或操纵以表达AID以进一步增强超敏性。 这些方法可用于在针对感兴趣的抗原的免疫球蛋白基因内产生遗传多样性，以产生具有增强的生化活性的改变的抗体。 此外，这些方法可用于产生具有增加的抗体产生水平的产生抗体的细胞。
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49.发明申请Methods For Generating Enhanced Antibody-Producing Cell Lines With Improved Growth Characteristics 审中-公开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
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。
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50.发明授权Methods for isolating novel antimicrobial agents from hypermutable mammalian cells 有权从高可变性哺乳动物细胞中分离新的抗微生物剂的方法公开(公告)号：US07223598B2
公开(公告)日：2007-05-29
申请号：US11235037
申请日：2005-09-26
IPC分类号： C12N15/01
CPC分类号： C07K14/47 , C12N15/01 , C12N15/102
摘要： Dominant-negative alleles of human mismatch repair genes can be used to generate hypermutable cells and organisms. By introducing these genes into mammalian cells new cell lines with novel and useful properties can be prepared more efficiently than by relying on the natural rate of mutation or introduction of mutations by chemical mutagens. These methods are useful for generating novel and highly active antimicrobial molecules as well as superior antimicrobial agents from pre-existing chemicals. These methods are also useful for generating cell lines expressing novel antimicrobials that are useful for pharmaceutical manufacturing.
摘要翻译： 人类错配修复基因的显性阴性等位基因可用于产生超可变细胞和生物体。 通过将这些基因引入哺乳动物细胞，可以比通过依赖于天然的突变率或通过化学诱变剂引入突变更有效地制备具有新颖和有用性质的新细胞系。 这些方法可用于产生新的和高活性的抗微生物分子以及来自预先存在的化学物质的优良的抗微生物剂。 这些方法也可用于产生表达可用于药物制造的新型抗微生物剂的细胞系。
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