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1. 发明申请

WO0198520A8 TRANSGENICALLY PRODUCED PLATELET DERIVED GROWTH FACTOR 审中-公开
标题翻译：转移生产板材衍生生长因子
公开(公告)号：WO0198520A8
公开(公告)日：2003-03-27
申请号：PCT/US0141044
申请日：2001-06-19
申请人： GENZYME TRANSGENICS CORP , ECHELARD YANN , MEADE HARRY , EICHNER WOLFRAM , SOMMERMEYER KLAUS
发明人： ECHELARD YANN , MEADE HARRY , EICHNER WOLFRAM , SOMMERMEYER KLAUS
IPC分类号： C12N15/09 , A61K38/00 , C07K14/49 , C12P21/00 , A01K67/00 , A61K38/24 , C07H21/04 , C12N15/00 , A23C
CPC分类号： C07K14/49 , A01K2217/05 , A61K38/00
摘要： The invention features transgenically produced PDGF, e.g., transgenically produced PDGF which is expressed in the milk of a transgenic mammal, and is present in the milk in active form, e.g., as a dimer. The invention also features methods of producing transgenic PDGF, transgenic animals capable of expressing PDGF, and nucleic acid sequences encoding PDGF, e.g., nucleic acid sequences encoding PDGF, under the control of a mammary gland specific promoter.
摘要翻译：本发明具有转基因产生的PDGF，例如在转基因哺乳动物的乳中表达的转基因产生的PDGF，并且以活性形式存在于例如二聚体的乳中。本发明还涉及在乳腺特异性启动子控制下产生转基因PDGF，能够表达PDGF的转基因动物和编码PDGF的核酸序列，例如编码PDGF的核酸序列的方法。

2. 发明申请

WO2006088464A3 A METHOD OF USING AN ANTI-CD137 ANTIBODY AS AN AGENT FOR RADIOIMMUNOTHERAPY OR RADIOIMMUNODETECTION 审中-公开
标题翻译：使用抗CD137抗体作为放射免疫疗法或放射免疫测定法的方法
公开(公告)号：WO2006088464A3
公开(公告)日：2007-11-15
申请号：PCT/US2005005405
申请日：2005-02-18
申请人： GTC BIOTHERAPEUTICS INC , STROME SCOTT E , SCHINDLER DANIEL , CHEN LIEPING , MEADE HARRY , ECHELARD YANN
发明人： STROME SCOTT E , SCHINDLER DANIEL , CHEN LIEPING , MEADE HARRY , ECHELARD YANN
IPC分类号： A61K39/395 , C07K16/00
CPC分类号： C07K16/2878 , A61K47/6817 , A61K47/6829 , A61K47/6849 , A61K51/1027 , A61K2039/507 , C07K2317/12 , C07K2317/74 , C07K2317/75
摘要： The current invention relates to the development and methods of use of a recombinant agonistic antibody anti-human CD137, and glycosylation variants thereof. These antibodies act as anti-cancer agents and/or immune modulators that are effective in shrinking solid tumors or other cancerous indications and preventing their recurrence. The types of cancer for which the contemplated antibody is effective in treating also include leukemia and lymphoma. In a preferred imbodiment the recombinant antibodies of the current invention were produced in and purified from the milk of transgenic animals. In another preferred embodiment of the current invention the agonistic anti-CD137 antibodies of the invention can be conjugated to radionuclides for radioimmunodetection or radioimmunotherapeutic purposes, or conjugated to a toxin for enhanced therapeutic treatment of various cancers.
摘要翻译：本发明涉及重组激动抗体抗人CD137及其糖基化变体的开发和使用方法。这些抗体作为有效减少实体瘤或其他癌症适应症并防止其复发的抗癌剂和/或免疫调节剂。预期抗体对其治疗有效的癌症类型还包括白血病和淋巴瘤。在优选的实施方案中，本发明的重组抗体在转基因动物的牛奶中制备和纯化。在本发明的另一个优选实施方案中，本发明的激动性抗CD137抗体可以与放射性核素缀合以用于放射免疫检测或放射免疫治疗目的，或与毒素缀合以增强各种癌症的治疗性治疗。

3. 发明申请

WO9920766A3 NOVEL MODIFIED NUCLEIC ACID SEQUENCES AND METHODS FOR INCREASING mRNA LEVELS AND PROTEIN EXPRESSION IN CELL SYSTEMS 审中-公开
标题翻译：用于增加细胞系统中mRNA水平和蛋白质表达的新修饰的核酸序列和方法
公开(公告)号：WO9920766A3
公开(公告)日：1999-09-02
申请号：PCT/US9822225
申请日：1998-10-20
申请人： GENZYME TRANSGENICS CORP
发明人： CHEN LI HOW , MEADE HARRY
IPC分类号： A01K67/027 , A61K35/76 , A61K39/00 , A61K39/012 , A61K39/12 , A61K48/00 , C07H21/04 , C07K14/445 , C07K14/47 , C12N1/21 , C12N5/10 , C12N15/09 , C12N15/30 , C12N15/67 , C12N15/74 , C12N15/85 , C12P19/34
CPC分类号： C12N15/8509 , A01K67/0275 , A01K2217/05 , A01K2227/10 , A01K2227/105 , A01K2267/01 , A61K39/00 , A61K48/00 , A61K2039/51 , A61K2039/53 , C07K14/445 , C07K14/4732 , C07K2319/00 , C07K2319/02 , C12N15/67 , C12N2830/008
摘要： The invention provides modified recombinant nucleic acid sequences (preferably DNA) and methods for increasing the mRNA levels and protein expression of proteins which are known to be, or are likely to be, difficult to express in cell culture systems, mammalian cell culture systems, or in transgenic animals. The preferred "difficult" protein candidates for expression using the recombinant techniques of the invention are those proteins derived from heterologous cells preferably those of lower organisms such as parasites, bacteria, and virus, having DNA coding sequences comprising high overall AT content or AT rich regions and/or mRNA instability motifs and/or rare codons relative to the recombinant expression system to be used.
摘要翻译：本发明提供了修饰的重组核酸序列（优选DNA）和用于增加已知或很可能难以在细胞培养系统，哺乳动物细胞培养系统或者哺乳动物细胞培养系统中表达的蛋白质的mRNA水平和蛋白质表达的方法在转基因动物中。使用本发明重组技术表达的优选“困难”候选蛋白质是那些源自异源细胞的蛋白质，优选那些具有包含高总体AT含量或AT富含区域的DNA编码序列的低等生物体如寄生虫，细菌和病毒的蛋白质和/或相对于待使用的重组表达系统的mRNA不稳定性基序和/或稀有密码子。

4. 发明申请

WO9920774A3 NOVEL MODIFIED MSP-1 NUCLEIC ACID SEQUENCES AND METHODS FOR INCREASING mRNA LEVELS AND PROTEIN EXPRESSION IN CELL SYSTEMS 审中-公开
标题翻译：用于增加细胞系统中mRNA水平和蛋白质表达的新型修饰的MSP-1核酸序列和方法
公开(公告)号：WO9920774A3
公开(公告)日：1999-08-26
申请号：PCT/US9822226
申请日：1998-10-20
申请人： GENZYME TRANSGENICS CORP
发明人： CHEN LI HOW , MEADE HARRY
IPC分类号： A01K67/027 , A61K35/76 , A61K39/00 , A61K39/012 , A61K39/12 , A61K48/00 , C07H21/04 , C07K14/445 , C07K14/47 , C12N1/21 , C12N5/10 , C12N15/09 , C12N15/30 , C12N15/67 , C12N15/74 , C12N15/85 , C12P19/34
CPC分类号： C12N15/8509 , A01K67/0275 , A01K2217/05 , A01K2227/10 , A01K2227/105 , A01K2267/01 , A61K39/00 , A61K48/00 , A61K2039/51 , A61K2039/53 , C07K14/445 , C07K14/4732 , C07K2319/00 , C07K2319/02 , C12N15/67 , C12N2830/008
摘要： The invention provides modified recombinant nucleic acid sequences (preferably DNA) and methods for increasing the mRNA levels and protein expression of malarial surface protein MSP-1 which is known to be difficult to express in cell culture systems, mammalian cell culture systems, or in transgenic animals. The preferred protein candidates for expression using the recombinant techniques of the invention are MSP-1 proteins expressed from DNA coding sequences comprising reduced overall AT content or AT rich regions and/or mRNA instability motifs and/or rare codons relative to the native MSP-1 gene.
摘要翻译：本发明提供了修饰的重组核酸序列（优选DNA）和用于增加已知难以在细胞培养系统，哺乳动物细胞培养系统或转基因中表达的疟疾表面蛋白MSP-1的mRNA水平和蛋白质表达的方法动物。使用本发明的重组技术进行表达的优选候选蛋白质是从编码序列表达的MSP-1蛋白质，所述DNA编码序列相对于天然MSP-1包含总体AT含量降低或AT富集区和/或mRNA不稳定性基序和/或稀有密码子基因。

5. 发明申请

WO2005024044A2 METHOD FOR THE PRODUCTION OF FUSION PROTEINS IN TRANSGENIC MAMMAL MILK 审中-公开
标题翻译：在转基因哺乳动物奶中生产融合蛋白的方法
公开(公告)号：WO2005024044A2
公开(公告)日：2005-03-17
申请号：PCT/US2004029128
申请日：2004-09-03
申请人： GTC BIOTHERAPEUTICS INC , MEADE HARRY , COX GEOFFREY F
发明人： MEADE HARRY , COX GEOFFREY F
IPC分类号： A01N43/04 , A61K38/00 , C07H21/04 , C07K1/00 , C12N5/00 , C12N15/00 , C12P21/00 , C12Q20060101 , C12Q
CPC分类号： C12N15/62 , A01K2217/05 , A01K2217/052 , A01K2227/101 , A01K2267/01 , C12N15/8509 , C12N2830/008 , C12N2830/40 , C12N2830/85
摘要： Desirable fusion proteins can be produced in and purified from the milk of transgenic animals. The peptides are made as fusion proteins with a suitable fusion partner such as human alpha-fetoprotein. The fusion partner protein acts to promote and increase the half-life of the overall molecule as well as having therapeutic effects on its own. The fusion protein is typically produced through the use of transgenic animals and can be purified away from the now the milk or other bodily fluid of such an animal by an affinity purification method. A particular advantage of producing peptides via this route, in addition to the obvious advantages of high yield and biocompatibility, is that specific post-translational modifications, such as carboxy terminal amidation, can be performed in the mammary gland. Biologically active polypeptides comprising a therapeutically active polypeptide fused to human alpha-fetoprotein fragment or a variant thereof, methods for the preparation thereof, nucleotide sequences encoding such fusion polypeptides, expression cassettes comprising such nucleotide sequences, self-replicating plasmids containing such expression cassettes, and pharmaceutical compositions containing said fusion polypeptides.
摘要翻译：理想的融合蛋白可以在转基因动物的乳中产生和纯化。该肽被制成与合适融合伴侣如人甲胎蛋白的融合蛋白。融合配偶体蛋白起到促进和增加整个分子的半衰期以及自身具有治疗效果的作用。通常通过使用转基因动物产生融合蛋白，并且可以通过亲和纯化方法从现在的这种动物的奶或其他体液中纯化融合蛋白。除了具有高收率和生物相容性的明显优点之外，通过该途径产生肽的特别优势在于可以在乳腺中进行特定的翻译后修饰，例如羧基末端酰胺化。包含与人甲胎蛋白片段或其变体融合的治疗活性多肽的生物活性多肽，其制备方法，编码此类融合多肽的核苷酸序列，包含此类核苷酸序列的表达盒，含有此类表达盒的自我复制质粒和含有该融合多肽的药物组合物。

6. 发明申请

WO2005079232A2 A METHOD FOR THE PRODUCTION OF AN ERYTHROPOIETIN ANALOG-HUMAN IgG FUSION PROTEINS IN TRANSGENIC MAMMAL MILK 审中-公开
标题翻译：一种在转基因乳制品中生产人类肝细胞模型人IgG融合蛋白的方法
公开(公告)号：WO2005079232A2
公开(公告)日：2005-09-01
申请号：PCT/US2005003625
申请日：2005-02-04
申请人： GTC BIOTHERAPEUTICS INC , MEADE HARRY , KRANE IAN
发明人： MEADE HARRY , KRANE IAN
IPC分类号： A01K67/027 , A61K39/395 , C07H21/04 , C07K14/505 , C12N15/85 , C12P21/04
CPC分类号： C12N15/8509 , A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2227/102 , A01K2227/105 , A01K2227/30 , A01K2267/01 , C07H21/04 , C07K14/505 , C07K2319/30 , C07K2319/75
摘要： Erythropoietin analog-human IgG fusion protein (EPOa-IgG) fusion protein and methods of making and using the fusion protein.
摘要翻译：红细胞生成素类似物 - 人IgG融合蛋白（EPOa-IgG）融合蛋白以及制备和使用融合蛋白的方法。

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