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1. 发明申请

WO1992022645A1 TRANSGENIC IMMUNODEFICIENT NON-HUMAN ANIMALS 审中-公开
标题翻译：转基因免疫非人类动物
公开(公告)号：WO1992022645A1
公开(公告)日：1992-12-23
申请号：PCT/US1992004823
申请日：1992-06-15
申请人： GENPHARM INTERNATIONAL , TERHORST, Cornelis, P. , HUANG, Manley, T., F.
发明人： GENPHARM INTERNATIONAL
IPC分类号： C12N15/00
CPC分类号： C12N15/8509 , A01K67/0271 , A01K67/0276 , A01K2217/05 , A01K2217/075 , A01K2217/30 , A01K2227/105 , A01K2267/0381 , C07K14/34 , C07K14/7051
摘要： Transgenic non-human animals having genotypes comprising a first DNA sequence encoding an expression regulation sequence for a lymphoid gene operably linked to DNA encoding a lethal polypeptide. Also included are transgenic animals having genotypes comprising the substitution, deletion or insertion of one or more nucleotides in at least one endogenous allele of a CD3-type gene. The transgenic non-human animals have phenotypes characterized by immunodeficiency in at least one function of a lymphoid cell. Such phenotypes include depletion of one or more lymphoid cell types such as T-cells, NK cells, large granular lymphocytes, and/or B-cells. The invention also provides transgenic immunodeficient animals containing a xenograft characterized by a phenotype wherein the animal has an enhanced ability to maintain the xenograft as compared to the maintenance of the xenograft in the species from which the transgenic animal is derived.
摘要翻译：具有基因型的转基因非人动物包含编码与编码致死多肽的DNA可操作地连接的淋巴样基因的表达调控序列的第一DNA序列。还包括具有基因型的转基因动物，其包含在CD3型基因的至少一个内源等位基因中取代，缺失或插入一个或多个核苷酸。转基因非人动物具有以淋巴细胞的至少一种功能为特征的免疫缺陷表型。这种表型包括一种或多种淋巴细胞类型的消耗，例如T细胞，NK细胞，大颗粒淋巴细胞和/或B细胞。本发明还提供了转基因免疫缺陷动物，其含有特征在于表型的异种移植物，其中与在转基因动物得到的物种中的异种移植物的维持相比，该动物具有增强的维持异种移植物的能力。

2. 发明申请

WO1991008216A1 PRODUCTION OF RECOMBINANT POLYPEPTIDES BY BOVINE SPECIES AND TRANSGENIC METHODS 审中-公开
标题翻译：通过牛肉种和转基因方法生产重组多糖
公开(公告)号：WO1991008216A1
公开(公告)日：1991-06-13
申请号：PCT/US1990006874
申请日：1990-11-30
申请人： GENPHARM INTERNATIONAL
发明人： GENPHARM INTERNATIONAL , HEYNEKER, Herbert, L. , DEBOER, Herman, A. , STRIJKER, Rein , PLANTENBURG, Gerard , LEE, Sang, He
IPC分类号： C07H21/00
CPC分类号： A01K67/0278 , A01K67/0275 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2227/101 , A01K2227/105 , A01K2267/01 , A23C9/20 , C07K14/4732 , C07K14/765 , C07K14/79 , C12N9/6464 , C12N15/8509 , C12Y304/21069
摘要： A transgene for producing recombinant polypeptides in the milk of transgenic bovine species comprises at least one expression regulation sequence, a secretory DNA sequence encoding a secretory signal which is functional in mammary secretory cells of the bovine species and a recombinant DNA sequence encoding the recombinant polypeptides. A method for producing transgenic bovine species comprises introducing the above transgene into an embryonal target cell of a bovine species, transplanting the transgenic embryonic target cell formed thereby into a recipient bovine parent and identifying at least one female offspring which is capable of producing the recombinant polypeptide in its milk. The invention also includes transgenic bovine species capable of producing recombinant polypeptides in transgenic milk as well as the milk from such transgenic bovine species and food formulations containing one or more recombinant polypeptide. A method for producing transgenic non-human mammals having a desirable phenotype comprises first methylating a transgene followed by introduction into fertilized oocytes. The oocytes are then cultured to form preimplantation embryos. Thereafter, at least one cell is removed from each of the pre-implantation embryos and the DNA digested with a restriction endonuclease capable of cleaving the methylated transgene but incapable of cleaving the unmethylated form of the transgene.
摘要翻译：用于在转基因牛物种的乳中产生重组多肽的转基因包括至少一种表达调控序列，编码在牛物种的乳腺分泌细胞中有功能的分泌信号的分泌型DNA序列和编码重组多肽的重组DNA序列。一种生产转基因牛物种的方法包括将上述转基因导入牛种的胚胎靶细胞，将由此形成的转基因胚胎靶细胞移植到接受者的母本中，鉴定能产生重组多肽的至少一个雌性后代在它的牛奶。本发明还包括能够在转基因乳中产生重组多肽的转基因牛物种以及来自这种转基因牛物种的乳和含有一种或多种重组多肽的食物制剂。用于产生具有所需表型的转基因非人哺乳动物的方法包括首先将转基因甲基化，然后引入受精卵母细胞。然后培养卵母细胞以形成植入前胚胎。此后，从每个植入前胚胎中移出至少一个细胞，并用能够切割甲基化的转基因而不能切割未甲基化形式的转基因的限制性内切核酸酶消化的DNA。

3. 发明申请

WO1990006359A1 TRANSGENIC NON-HUMAN ANIMALS DEPLETED IN A MATURE LYMPHOCYTIC CELL-TYPE 审中-公开
标题翻译：在一个成熟的淋巴细胞类型中转移的转基因非人动物
公开(公告)号：WO1990006359A1
公开(公告)日：1990-06-14
申请号：PCT/US1989005210
申请日：1989-11-22
申请人： GENPHARM INTERNATIONAL
发明人： GENPHARM INTERNATIONAL , KRIMPENFORT, Paulus, Jacobus, Angelinus , BERNS, Antonius, Josef, Maria
IPC分类号： C12N05/00
CPC分类号： A01K67/0275 , A01K67/0276 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2217/075 , A01K2227/105 , A01K2267/03 , A01K2267/0337 , A01K2267/0381 , C07K14/7051 , C07K16/00 , C07K2317/77 , C12N15/8509 , C12N2830/008
摘要： Transgenic non-human animals having a phenotype characterized by the substantial depletion of a mature lymphocytic cell type otherwise naturally occurring in the species from which the transgenic animal is derived. The phenotype is conferred in the transgenic animal by a transgene contained in at least the precursor stem cell of the lymphocytic cell type which is depleted. The transgene comprises a DNA sequence encoding a lymphatic polypeptide variant which inhibits maturation of the lymphocytic cell type.

4. 发明申请

WO1998024884A1 TRANSGENIC NON-HUMAN ANIMALS CAPABLE OF PRODUCING HETEROLOGOUS ANTIBODIES 审中-公开
标题翻译：可产生异位抗体的转基因非人动物
公开(公告)号：WO1998024884A1
公开(公告)日：1998-06-11
申请号：PCT/US1997021803
申请日：1997-12-01
申请人： GENPHARM INTERNATIONAL
发明人： GENPHARM INTERNATIONAL , LONBERG, Nils , KAY, Robert, M.
IPC分类号： C12N05/00
CPC分类号： C12N15/8509 , A01K67/0276 , A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2217/072 , A01K2217/075 , A01K2227/105 , A01K2267/01 , A01K2267/025 , A61K38/00 , C07K14/7051 , C07K16/00 , C07K16/2812 , C07K16/3007 , C07K16/4266 , C07K16/4291 , C07K16/44 , C07K16/462 , C07K2317/21 , C07K2317/24 , C07K2317/52 , C07K2317/56 , C07K2317/76 , C07K2319/00 , C12N5/163 , C12N15/00 , C12N15/113 , C12N15/85 , C12N15/87 , C12N15/90 , C12N15/907 , C12N2800/206 , C12N2800/70 , C12N2830/30 , C12N2830/36 , C12N2830/85
摘要： The invention relates to transgenic non-human animals capable of producing heterologous antibodies and methods for producing human sequence antibodies which bind to human antigens with substantial affinity.
摘要翻译：本发明涉及能够产生异源抗体的转基因非人动物和用于产生具有显着亲和力结合人抗原的人序列抗体的方法。

5. 发明申请

WO1992003917A1 HOMOLOGOUS RECOMBINATION IN MAMMALIAN CELLS 审中-公开
标题翻译：妈妈细胞中的同源重组
公开(公告)号：WO1992003917A1
公开(公告)日：1992-03-19
申请号：PCT/US1991005917
申请日：1991-08-28
申请人： GENPHARM INTERNATIONAL , KAY, Robert, M. , BERNS, Anton , KRIMPENFORT, Paul , PIEPER, Frank , STRIJKER, Rein
发明人： GENPHARM INTERNATIONAL
IPC分类号： A01H01/00
CPC分类号： A01K67/0275 , A01K2217/05 , C07K14/765 , C07K14/79 , C07K16/00 , C12N15/85 , C12N15/87 , C12N15/907 , C12N2800/206 , C12N2830/00 , C12N2830/85
摘要： The invention relates to methods for intracellularly producing DNA segments by homologous recombination of smaller overlapping DNA fragments and transgenic mammalian cells and transgenic non-human mammals produced by such methods.
摘要翻译：本发明涉及通过较小的重叠DNA片段和转基因哺乳动物细胞以及通过这些方法产生的转基因非人哺乳动物的同源重组来细胞内产生DNA片段的方法。

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