公开(公告)号：US20050266463A1

公开(公告)日：2005-12-01

申请号：US11128420

申请日：2005-05-13

申请人： Nicholas Nicolaides ,  Luigi Grasso ,  Phillip Sass ,  Ken Kinzler ,  Bert Vogelstein

发明人： Nicholas Nicolaides ,  Luigi Grasso ,  Phillip Sass ,  Ken Kinzler ,  Bert Vogelstein

IPC分类号： C07K14/415 ,  C12N15/10 ,  C12N15/29 ,  C12N15/82

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.

公开(公告)号：US20060194236A1

公开(公告)日：2006-08-31

申请号：US11360995

申请日：2006-02-24

申请人： Nicholas Nicolaides ,  Philip Sass ,  Luigi Grasso ,  Bert Vogelstein ,  Kenneth Kinzler

发明人： Nicholas Nicolaides ,  Philip Sass ,  Luigi Grasso ,  Bert Vogelstein ,  Kenneth Kinzler

IPC分类号： C12Q1/68 ,  C12N1/21 ,  C12N15/74

CPC分类号： C12N15/1024 ,  C12N15/01 ,  C12N15/102

摘要： Bacteria are manipulated to create desirable output traits using dominant negative alleles of mismatch repair proteins. Enhanced hypermutation is achieved by combination of mismatch repair deficiency and exogenously applied mutagens. Stable bacteria containing desirable output traits are obtained by restoring mismatch repair activity to the bacteria.

公开(公告)号：US20050188428A1

公开(公告)日：2005-08-25

申请号：US10873114

申请日：2004-06-23

申请人： Nicholas Nicolaides ,  Philip Sass ,  Luigi Grasso ,  Bert Vogelstein ,  Kenneth Kinzler

发明人： Nicholas Nicolaides ,  Philip Sass ,  Luigi Grasso ,  Bert Vogelstein ,  Kenneth Kinzler

IPC分类号： C07K14/47 ,  C12N15/01 ,  C12N15/10 ,  A01K67/027 ,  C12N15/85

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。

公开(公告)号：US20050272140A1

公开(公告)日：2005-12-08

申请号：US11188743

申请日：2005-07-26

申请人： Nicholas Nicolaides ,  Philip Sass ,  Luigi Grasso ,  Bert Vogelstein ,  Kenneth Kinzler

发明人： Nicholas Nicolaides ,  Philip Sass ,  Luigi Grasso ,  Bert Vogelstein ,  Kenneth Kinzler

IPC分类号： C12N1/18 ,  C12N1/19 ,  C12N15/74 ,  C12N15/81

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 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。 具有有缺陷的错配修复系统的酵母细胞是超可变的，但是在选择所需的突变酵母菌株之后，可以通过将不匹配修复系统恢复到适当的功能来使它们变得遗传稳定。

公开(公告)号：US6146894A

公开(公告)日：2000-11-14

申请号：US059461

申请日：1998-04-14

申请人： Nicholas Nicolaides ,  Bert Vogelstein ,  Kenneth W. Kinzler

发明人： Nicholas Nicolaides ,  Bert Vogelstein ,  Kenneth W. Kinzler

IPC分类号： C07K14/47 ,  C12N15/01 ,  C12N15/10 ,  C12N15/00

CPC分类号： C12N15/1024 ,  C07K14/47 ,  A01K2217/05

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.

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。

公开(公告)号：US20060204506A1

公开(公告)日：2006-09-14

申请号：US11373546

申请日：2006-03-09

申请人： Wolfgang Ebel ,  Luigi Grasso ,  Nicholas Nicolaides ,  Philip Sass ,  Eric Routhier

发明人： Wolfgang Ebel ,  Luigi Grasso ,  Nicholas Nicolaides ,  Philip Sass ,  Eric Routhier

IPC分类号： A61K39/395 ,  C07H21/04 ,  C12P21/06 ,  C12N5/06 ,  C07K16/30

CPC分类号： C07K16/28 ,  A61K39/3955 ,  A61K45/06 ,  A61K2039/505 ,  C07K16/30 ,  C07K16/3069 ,  C07K2317/56 ,  C07K2317/732 ,  C07K2317/77

摘要： This invention relates to the use of monoclonal and polyclonal antibodies that specifically bind to and become internalized by mesothelin-positive cells and also induce an immune effector activity such as antibody dependent cellular cytotoxicity. The antibodies are useful in specific delivery of pharmacologic agents to mesothelin expressing cells as well as eliciting an immune-effector activity particularly on tumor cells and precursors. The invention is also related to cells expressing the monoclonal antibodies, polyclonal antibodies, antibody derivatives, such as human, humanized, and chimeric monoclonal antibodies, antibody fragments, mammalian cells expressing the monoclonal antibodies, derivatives and fragments, and methods of treating cancer using the antibodies, derivatives and fragments.

公开(公告)号：US07297837B1

公开(公告)日：2007-11-20

申请号：US09558149

申请日：2000-04-26

申请人： Nicholas Nicolaides ,  Bert Vogelstein ,  Kenneth W. Kinzler

发明人： Nicholas Nicolaides ,  Bert Vogelstein ,  Kenneth W. Kinzler

IPC分类号： A01K67/027 ,  C12N15/00 ,  G01N33/00 ,  A01K67/00 ,  A01K67/33

CPC分类号： C12N15/1024 ,  A01K2217/05 ,  C07K14/47

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.

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。

公开(公告)号：US07829338B2

公开(公告)日：2010-11-09

申请号：US11907338

申请日：2007-10-11

申请人： Nicholas Nicolaides ,  Bert Vogelstein ,  Kenneth Kinzler

发明人： Nicholas Nicolaides ,  Bert Vogelstein ,  Kenneth Kinzler

IPC分类号： C12N15/00 ,  C12N5/00 ,  C12N5/02 ,  C12N15/74 ,  C12Q1/68

CPC分类号： C12N15/1024 ,  A01K2217/05 ,  C07K14/47

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.

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。

公开(公告)号：US20060239911A1

公开(公告)日：2006-10-26

申请号：US11410472

申请日：2006-04-24

申请人： Nicholas Nicolaides ,  Luigi Grasso ,  Philip Sass

发明人： Nicholas Nicolaides ,  Luigi Grasso ,  Philip Sass

IPC分类号： A61K51/00 ,  A61K39/395 ,  G01N33/574 ,  C07K16/46 ,  C07K16/30

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.

公开(公告)号：US20060121541A1

公开(公告)日：2006-06-08

申请号：US11292634

申请日：2005-12-02

申请人： Luigi Grasso ,  Gaurav Deshmukh ,  Nicholas Nicolaides ,  Philip Sass

发明人： Luigi Grasso ,  Gaurav Deshmukh ,  Nicholas Nicolaides ,  Philip Sass

IPC分类号： G01N33/574 ,  C12N5/06 ,  C12N5/08

CPC分类号： G01N33/574 ,  C07K16/2851 ,  G01N33/56966 ,  G01N33/57492 ,  G01N2333/515 ,  G01N2333/70596 ,  G01N2500/00 ,  G01N2800/10 ,  G01N2800/16 ,  G01N2800/24

摘要： Monoclonal antibodies and other proteins that specifically bind to cells positive for endosialin are provided. The antibodies and proteins are useful in the isolation of endosialin-positive cells, particularly cells associated with neovascularization associated with cancer and neovascular disease. The invention is also related to cells that are isolated using monoclonal antibodies; antibody derivatives, such as chimeric and humanized monoclonal antibodies; antibody fragments; mammalian cells expressing the monoclonal antibodies, derivatives and fragments; and methods of detecting and isolating endosialin-positive cells using the antibodies, derivatives and fragments.

摘要翻译： 提供了单克隆抗体和其他特异性结合内皮素的阳性细胞的蛋白质。 抗体和蛋白质可用于分离内皮唾液酸阳性细胞，特别是与与癌症和新血管病相关的新生血管形成相关的细胞。 本发明还涉及使用单克隆抗体分离的细胞; 抗体衍生物，例如嵌合和人源化单克隆抗体; 抗体片段; 表达单克隆抗体，衍生物和片段的哺乳动物细胞; 以及使用抗体，衍生物和片段检测和分离内皮唾液酸 - 阳性细胞的方法。