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1. 发明授权

US5986079A Expression of pace in host cells and methods of use thereof 失效
公开(公告)号：US5986079A
公开(公告)日：1999-11-16
申请号：US480382
申请日：1995-06-07
申请人： Philip J. Barr , Anthony J. Brake , Randal J. Kaufman , Patricia Tekamp-Olson , Louise Wasley , Polly A. Wong
发明人： Philip J. Barr , Anthony J. Brake , Randal J. Kaufman , Patricia Tekamp-Olson , Louise Wasley , Polly A. Wong
IPC分类号： C12N5/10 , C07K14/755 , C12N9/50 , C12N9/64 , C12N15/09 , C12N15/57 , C12P21/02 , C12N15/79 , C12N15/85
CPC分类号： C12N9/6454 , C07K14/755
摘要： Compositions and methods are provided for endopeptidase production and for enhanced efficiencies of processing heterologous precursor polypeptides to mature polypeptides, including proteins requiring gamma-carboxylation for biological activity. These compositions and methods utilize recombinant PACE, a mammalian endopeptidase that is specific for dibasic amino acid sites.

2. 发明授权

US5965425A Expression of pace in host cells and methods of use thereof 失效
标题翻译：宿主细胞中步调的表达及其使用方法
公开(公告)号：US5965425A
公开(公告)日：1999-10-12
申请号：US745880
申请日：1996-11-08
申请人： Philip J. Barr , Anthony J. Brake , Randal J. Kaufman , Patricia Tekamp-Olson , Louise Wasley , Polly A. Wong
发明人： Philip J. Barr , Anthony J. Brake , Randal J. Kaufman , Patricia Tekamp-Olson , Louise Wasley , Polly A. Wong
IPC分类号： C12N5/10 , C07K14/755 , C12N9/50 , C12N9/64 , C12N15/09 , C12N15/57 , C12P21/02 , C12N9/48 , C12N15/79
CPC分类号： C12N9/6454 , C07K14/755
摘要： Compositions and methods are provided for endopeptidase production and for enhanced efficiencies of processing heterologous precursor polypeptides to mature polypeptides, including proteins requiring gamma-carboxylation for biological activity. These compositions and methods utilize recombinant PACE, a mammalian endopeptidase that is specific for dibasic amino acid sites.
摘要翻译：提供用于内肽酶生产的组合物和方法，以及提高加工异源前体多肽对成熟多肽（包括需要γ-羧化生物活性的蛋白质）的效率。这些组合物和方法利用重组PACE，一种特异于二元氨基酸位点的哺乳动物内肽酶。

3. 发明授权

US5460950A Expression of PACE in host cells and methods of use thereof 失效
标题翻译： PACE在宿主细胞中的表达及其使用方法
公开(公告)号：US5460950A
公开(公告)日：1995-10-24
申请号：US885972
申请日：1992-05-20
申请人： Philip J. Barr , Anthony J. Brake , Randal J. Kaufman , Louise Wasley , Patricia Tekamp-Olson , Polly A. Wong
发明人： Philip J. Barr , Anthony J. Brake , Randal J. Kaufman , Louise Wasley , Patricia Tekamp-Olson , Polly A. Wong
IPC分类号： C12N5/10 , C07K14/755 , C12N9/50 , C12N9/64 , C12N15/09 , C12N15/57 , C12P21/02 , C12N15/00 , C12N15/81 , C12N15/85
CPC分类号： C12N9/6454 , C07K14/755
摘要： Compositions and methods are provided for endopeptidase production and for enhanced efficiencies of processing heterologous precursor polypeptides to mature polypeptides, including proteins requiring gamma-carboxylation for biological activity. These compositions and methods utilize recombinant PACE, a mammalian endopeptidase that is specific for dibasic amino acid sites.
摘要翻译：提供用于内肽酶生产的组合物和方法，以及提高加工异源前体多肽对成熟多肽（包括需要γ-羧化生物活性的蛋白质）的效率。这些组合物和方法利用重组PACE，一种特异于二元氨基酸位点的哺乳动物内肽酶。

4. 发明授权

US4880734A Eukaryotic regulatable transcription 失效
标题翻译：真核调控转录
公开(公告)号：US4880734A
公开(公告)日：1989-11-14
申请号：US868639
申请日：1986-05-29
申请人： Rae L. Burke , Steven Rosenberg , Jeffrey R. Shuster , Patricia Tekamp-Olson , Pablo D. T. Valenzuela , Philip J. Barr
发明人： Rae L. Burke , Steven Rosenberg , Jeffrey R. Shuster , Patricia Tekamp-Olson , Pablo D. T. Valenzuela , Philip J. Barr
IPC分类号： C07K14/02 , C07K14/81 , C12N9/02 , C12N15/62 , C12N15/81
CPC分类号： C07K14/005 , C07K14/8125 , C12N15/62 , C12N15/81 , C12N9/0089 , C07K2319/00 , C07K2319/02 , C07K2319/40 , C07K2319/75 , C12N2730/10122
摘要： Methods and compositions are provided for efficient expression of genes in unicellular microoorganisms, particularly yeast. The systems involve an expression system employing transcriptional initiation regions from glycolytic enzymes, particularly a chimeric expression system, having a first region providing for regulatable or constitutive expression, a second region providing for transcriptional initiation, where regions one and two are not found joined together in functional relationship in nature, and optionally a sequence providing for a secretory leader and processing signal, where the expression cassette will be joined to a gene which may be homologous or heterologous to the host. The expression cassette can be used on an extrachromosomal element or integrated into the host genome, whereby continuous expression can be achieved or inducible expression is obtained, by virtue of the presence or absence of an inducer. Constructions may be provided, where structural genes may be introduced in reading frame with the cassette to provide for expression of the natural peptide, a fused peptide, or a peptide precursor.The S. cerevisiae strain AB110 (pAB24/P. vivax 1-5 was deposited at the A.T.C.C. on May 9, 1986, and given Accession No. 20797.
摘要翻译：提供了用于在单细胞微生物，特别是酵母中有效表达基因的方法和组合物。该系统涉及使用来自糖酵解酶，特别是嵌合表达系统的转录起始区的表达系统，其具有提供可调节或组成型表达的第一区域，提供转录起始的第二区域，其中未发现第一和第二区域连接在一起功能性关系，以及任选地提供分泌前导序列和处理信号的序列，其中表达盒将与可与宿主同源或异源的基因连接。表达盒可以在染色体外元件上使用或整合到宿主基因组中，由此可以通过诱导剂的存在或不存在来实现连续表达或获得诱导型表达。可以提供构建体，其中结构基因可以在盒子的阅读框中引入以提供天然肽，融合肽或肽前体的表达。酿酒酵母菌株AB110（pAB24 / P.vivax 1-5）于1986年5月9日保藏于A.T.C.C.，保藏号为20797。

5. 发明授权

US5089398A Enhanced yeast transcription employing hybrid GAPDH promoter region constructs 失效
标题翻译：使用混合GAPDH启动子区构建体增强酵母转录
公开(公告)号：US5089398A
公开(公告)日：1992-02-18
申请号：US380783
申请日：1989-07-18
申请人： Steven Rosenberg , Patricia Tekamp-Olson
发明人： Steven Rosenberg , Patricia Tekamp-Olson
IPC分类号： C07K14/02 , C07K14/81 , C12N9/02 , C12N15/81
CPC分类号： C07K14/005 , C07K14/8125 , C12N15/81 , C12N9/0089 , C07K2319/00 , C07K2319/02 , C07K2319/40 , C07K2319/61 , C07K2319/75 , C12N2730/10122
摘要： Yeast promoters of glycolytic enzymes are modified by isolating a fragment encompassing the RNA polymerase binding site and joining to the 5' end of this fragment a DNA sequence providing for enhanced inducible or constitutive transcription of a structural gene. Constructs are prepared for efficient expression of foreign genes in yeast.Yeast strains 2150-2-3 (pC1/1GAPSOD) and AB110 (pC1/1GAPATi9), producing human .alpha..sub.1 -antitrypsin and superoxide dismutase, were desposited at the A.T.C.C. on May 9, 1984 and given Accession Nos. 20708 and 20709, respectively; and 2150-2-3 (GAP5), 2150-2-3 (Pyk5) and 2150-2-3 (PHO5GAP1), expressing Hepatitis B surface antigen, were deposited at the A.T.C.C. on May 9, 1984 and given Accession Nos. 20705, 20706 and 20707, respectively.
摘要翻译：糖酵解酶的酵母启动子通过分离包含RNA聚合酶结合位点的片段并与该片段的5'末端连接提供结构基因的增强的诱导型或组成型转录的DNA序列来修饰。制备用于在酵母中有效表达外源基因的构建体。酵母菌株2150-2-3（pC1 / 1GAPSOD）和AB110（pC1 / 1GAPATi9），产生人α1-抗胰蛋白酶和超氧化物歧化酶，在A.T.C.C. 分别于1984年5月9日和第20708和20709年加入。和表达乙型肝炎表面抗原的2150-2-3（GAP5），2150-2-3（Pyk5）和2150-2-3（PHO5GAP1）在A.T.C.C. 分别于1984年5月9日，加拿大号20705,20706和20707。

6. 发明授权

US06706496B2 Method for expression of heterologous proteins in yeast 失效
标题翻译：在酵母中表达异源蛋白的方法
公开(公告)号：US06706496B2
公开(公告)日：2004-03-16
申请号：US09921398
申请日：2001-08-02
申请人： Patricia Tekamp-Olson
发明人： Patricia Tekamp-Olson
IPC分类号： C12N1500
CPC分类号： A61K38/1858 , A61K9/0014 , A61K9/06 , A61L26/0066 , A61L2300/414 , C07K14/49 , C07K14/65 , C07K2319/02 , C12N15/81
摘要： Compositions and methods for expression of heterologous mammalian proteins and their secretion in the biologically active mature form using a yeast host cell as the expression system are provided. Compositions of the invention are nucleotide sequences encoding a signal peptide sequence for a yeast secreted protein, an optional leader peptide sequence for a yeast secreted protein, a native propeptide leader sequence for a mature protein of interest, and a sequence for the mature protein of interest, all operably linked to a yeast promoter. Each of these elements is associated with a processing site recognized in vivo by a yeast proteolytic enzyme. Any or all of these processing sites may be a preferred processing site that has been modified or synthetically derived for more efficient cleavage in vivo. The compositions are useful in methods for expression of heterologous mammalian proteins and their secretion in the biologically active mature form. Particularly, vectors comprising these nucleotide coding sequences can be used to transform a yeast host cell, which can then be cultured and screened for secretion of the biologically active mature protein of interest.
摘要翻译：提供了使用酵母宿主细胞作为表达系统来表达异源哺乳动物蛋白质及其在生物活性成熟形式中的分泌的组合物和方法。本发明的组合物是编码酵母分泌蛋白质的信号肽序列，酵母分泌蛋白质的任选的前导肽序列，感兴趣的成熟蛋白质的天然前肽前导序列和感兴趣的成熟蛋白质的序列的核苷酸序列，全部可操作地连接到酵母启动子。这些元素中的每一个都与酵母蛋白水解酶在体内识别的处理位点相关联。这些处理位点中的任何一个或全部可以是经修饰或合成衍生的用于在体内更有效切割的优选的处理位点。该组合物可用于以生物活性成熟形式表达异源哺乳动物蛋白及其分泌的方法。特别地，包含这些核苷酸编码序列的载体可用于转化酵母宿主细胞，然后可将其培养和筛选以分泌目的生物活性成熟蛋白质。

7. 发明授权

US06448379B1 IL8 inhibitors 失效
标题翻译： IL8抑制剂
公开(公告)号：US06448379B1
公开(公告)日：2002-09-10
申请号：US08121105
申请日：1993-09-14
申请人： Patricia Tekamp-Olson , Guy Mullenbach , Mary Ellen Wernette-Hammond
发明人： Patricia Tekamp-Olson , Guy Mullenbach , Mary Ellen Wernette-Hammond
IPC分类号： C07K1600
CPC分类号： C07K16/2866 , A61K38/00 , A61K2039/505
摘要： Inhibitors, including antibodies, of IL8 binding to its receptors, that interact with the amino-terminal extracellular domain of the IL8 receptor and which compete with IL8 for receptor-binding, are disclosed. The inhibitors are useful modulators of IL8 receptor-mediated biological activity.
摘要翻译：公开了与IL8受体结合的IL8的抑制剂，其与IL8受体的氨基末端胞外结构域相互作用并与IL8竞争用于受体结合。抑制剂是IL8受体介导的生物活性的有用调节剂。

8. 发明授权

US6017731A Method for expression of heterologous proteins in yeast 失效
公开(公告)号：US6017731A
公开(公告)日：2000-01-25
申请号：US989251
申请日：1997-12-12
申请人： Patricia Tekamp-Olson , James P. Merryweather
发明人： Patricia Tekamp-Olson , James P. Merryweather
IPC分类号： A61K38/22 , A61K38/00 , A61K38/18 , A61P17/02 , C07K1/18 , C07K14/39 , C07K14/49 , C07K14/65 , C07K19/00 , C12N1/19 , C12N15/09 , C12N15/81 , C12P21/02 , C12N15/62
CPC分类号： A61K38/1858 , C07K14/49 , C07K14/65 , C12N15/81 , C07K2319/02
摘要： Compositions and methods for expression of heterologous mammalian proteins and their secretion in the biologically active mature form using a yeast host cell as the expression system are provided. Compositions of the invention are nucleotide sequences encoding a signal peptide sequence for a yeast secreted protein, an optional leader peptide sequence for a yeast secreted protein, a native propeptide leader sequence for a mature protein of interest, and a sequence for the mature protein of interest, all operably linked to a yeast promoter. Each of these elements is associated with a processing site recognized in vivo by a yeast proteolytic enzyme. Any or all of these processing sites may be a preferred processing site that has been modified or synthetically derived for more efficient cleavage in vivo. The compositions are useful in methods for expression of heterologous mammalian proteins and their secretion in the biologically active mature form. Particularly, vectors comprising these nucleotide coding sequences can be used to transform a yeast host cell, which can then be cultured and screened for secretion of the biologically active mature protein of interest.

9. 发明授权

US06436390B1 IL8 inhibitors 失效
公开(公告)号：US06436390B1
公开(公告)日：2002-08-20
申请号：US08487795
申请日：1995-06-07
申请人： Patricia Tekamp-Olson , Guy Mullenbach , Mary Ellen Wernette-Hammond
发明人： Patricia Tekamp-Olson , Guy Mullenbach , Mary Ellen Wernette-Hammond
IPC分类号： A61K4500
CPC分类号： C07K16/2866 , A61K38/00 , A61K2039/505
摘要： Inhibitors, including antibodies, of IL8 binding to its receptors, that interact with the amino-terminal extracellular domain of the IL8 receptor and which compete with IL8 for receptor-binding, are disclosed. The inhibitors are useful modulators of IL8 receptor-mediated biological activity.

10. 再颁专利

USRE37343E1 Expression and secretion of heterologous proteins in yeast employing truncated alpha-factor leader sequences 有权
标题翻译：使用截短的α因子前导序列在酵母中表达和分泌异源蛋白
公开(公告)号：USRE37343E1
公开(公告)日：2001-08-28
申请号：US09140858
申请日：1998-08-27
申请人： Patricia Tekamp-Olson
发明人： Patricia Tekamp-Olson
IPC分类号： C12N1562
CPC分类号： C12N15/81 , C07K14/39 , C07K14/62 , C07K14/65 , C07K2319/02
摘要： A yeast &agr;-factor expression system is provided comprised of a truncated leader sequence, containing the &agr;-factor signal peptide and one glycosylation site, linked by a processing site to a non-yeast protein-encoding sequence.
摘要翻译：提供酵母α因子表达系统，其包含截短的前导序列，其含有α-因子信号肽和一个糖基化位点，通过加工位点连接到非酵母蛋白质编码序列。

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