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61.发明授权Antibodies and methods for generating genetically altered antibodies with high affinity 有权用于产生具有高亲和力的遗传改变的抗体的抗体和方法公开(公告)号：US07671179B2
公开(公告)日：2010-03-02
申请号：US11746868
申请日：2007-05-10
IPC分类号： C07K16/18
CPC分类号： C12N15/01 , C07K16/00 , C07K16/4291 , C07K2317/56 , C07K2317/567 , C07K2317/92 , C12N15/1024
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 affinity of monoclonal antibodies and monoclonal antibodies with increased affinity.
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亲和力的单克隆抗体和单克隆抗体的亲和力的方法。
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62.发明申请Genetically Altered Anti-body Producing Cell Lines With Improved Antibody Characteristics 审中-公开基因改造的抗体生产细胞系具有改善的抗体特征公开(公告)号：US20100021996A1
公开(公告)日：2010-01-28
申请号：US12566167
申请日：2009-09-24
IPC分类号： C12N5/16
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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63.发明申请Antibodies With Immune Effector Activity And That Internalize In Folate Receptor Alpha-Positive Cells 有权具有免疫作用活性的抗体，并且在叶酸受体α阳性细胞内部化公开(公告)号：US20090324594A1
公开(公告)日：2009-12-31
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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64.发明授权Antibodies with immune effector activity and that internalize in endosialin-positive cells 有权具有免疫效应子活性的抗体，并且在内皮细胞内阳性细胞内部化公开(公告)号：US07615372B2
公开(公告)日：2009-11-10
申请号：US11410472
申请日：2006-04-24
IPC分类号： C12N15/85
CPC分类号： A61K39/39583 , A61K47/6825 , A61K47/6897 , A61K2039/505 , B82Y5/00 , C07K16/28 , C07K16/2851 , C07K2317/732 , 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 endosialin and to induce an immune effector activity such as antibody-dependent cellular cytotoxicity. The antibodies are useful in specific delivery of pharmacologic agents to endosialin-expressing cells as well as in eliciting an immune-effector activity particularly on tumor and neovascular cells and precursors. The invention is also related to nucleotides encoding the antibodies of the invention, cells expressing the antibodies; methods of detecting cancer and neovascular cells; and methods of treating cancer and neovascular disease using the antibodies, derivatives and fragments.
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，其通过表达内质网蛋白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。 抗体可用于特异性递送药物剂至表达唾液酸的细胞，以及引发免疫效应物特异性对肿瘤和新生血管细胞和前体的活性。 本发明还涉及编码本发明抗体的核苷酸，表达抗体的细胞; 检测癌症和新血管细胞的方法; 以及使用抗体，衍生物和片段治疗癌症和新生血管疾病的方法。
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65.发明申请METHODS FOR ISOLATING NOVEL ANTIMICROBIAL AGENTS FROM HYPERMUTABLE MAMMALIAN CELLS 有权从高可控性母体细胞中分离新型抗微生物剂的方法公开(公告)号：US20080182242A1
公开(公告)日：2008-07-31
申请号：US11736888
申请日：2007-04-18
IPC分类号： C12Q1/68
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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公开(公告)号：US20080176329A1
公开(公告)日：2008-07-24
申请号：US11930400
申请日：2007-10-31
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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公开(公告)号：US07319036B2
公开(公告)日：2008-01-15
申请号：US10873114
申请日：2004-06-23
CPC分类号： C12N15/1024 , 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 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. The enhanced rate of mutation can be further augmented using mutagens. Moreover, the hypermutability of mismatch repair deficient cells can be remedied to stabilize cells or mammals with useful mutations.
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。 使用诱变剂可以进一步增强突变率的增强。 此外，错配修复缺陷细胞的高度易失性可以补救以稳定具有有用突变的细胞或哺乳动物。
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公开(公告)号：US06921666B2
公开(公告)日：2005-07-26
申请号：US10641068
申请日：2003-08-15
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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公开(公告)号：US20110055964A1
公开(公告)日：2011-03-03
申请号：US12728958
申请日：2010-03-22
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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公开(公告)号：US20110224406A1
公开(公告)日：2011-09-15
申请号：US12752219
申请日：2010-04-01
IPC分类号： C07K14/715 , C07H21/04 , C07H21/02
CPC分类号： C12Q1/6883 , A61K38/00 , C07K14/7155 , C12Q2600/156
摘要： This invention relates to the diagnosis, treatment and methods for discovery of new therapeutics for atopic asthma and related disorders based on variants of Asthma Associated Factor 2. One embodiment of the invention is a variant of AAF2 wherein codon 173 is deleted resulting in the loss of glutamine 173 from the mature protein precursor. This single amino acid deletion results in a non-functional AAF2 protein and therefore the presence of this phenotype should be associated with less evidence of atopic asthma. Correspondingly, the lack of susceptibility to an asthmatic, atopic phenotype is characterized by the loss of glutamine at codon 171 The invention includes isolated DNA molecules which are variants of the wild type sequence as well as the proteins encoded by such DNA and the use of such DNA molecules and expressed protein in the diagnosis and treatment of atopic asthma.
摘要翻译： 本发明涉及用于发现基于哮喘相关因子2变体的特应性哮喘和相关病症的新治疗剂的诊断，治疗和方法。本发明的一个实施方案是AAF2的变体，其中密码子173缺失导致 来自成熟蛋白质前体的谷氨酰胺173。 该单个氨基酸缺失导致非功能性AAF2蛋白，因此该表型的存在应该与较少的特应性哮喘证据相关。 相应地，对哮喘，特应性表型的敏感性的缺乏的特征在于密码子171处的谷氨酰胺的丧失。本发明包括作为野生型序列的变体的分离的DNA分子以及由这样的DNA编码的蛋白质 DNA分子和表达蛋白在特应性哮喘的诊断和治疗中的应用。
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