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1. 发明授权

US4914026A Alpha factor leader sequence directed secretion of insulin 失效
标题翻译： α因子前导序列导向胰岛素分泌
公开(公告)号：US4914026A
公开(公告)日：1990-04-03
申请号：US922288
申请日：1986-10-23
申请人： Anthony J. Brake , Lawrence S. Cousens , Mickey S. Urdea , Pablo D. T. Valenzuela
发明人： Anthony J. Brake , Lawrence S. Cousens , Mickey S. Urdea , Pablo D. T. Valenzuela
IPC分类号： C07K14/62 , C12N15/17 , C12N15/62 , C12N15/81
CPC分类号： C07K14/62 , C12N15/625 , C12N15/81 , C07K2319/02 , C07K2319/036 , C07K2319/75
摘要： Methods and compositions are provided for efficient production of polypeptides having insulin activity. The proinsulin gene is joined to secretion and processing signals for expession and secretion in yeast. The product may be obtained in enhanced yield in the nutrient medium.Cell line AB103(PYinsl) was deposited at the A.T.C.C. on Apr. 6, 1983 and given Accession No. 20,670.
摘要翻译：提供了方法和组合物用于有效生产具有胰岛素活性的多肽。胰岛素原基因与分泌和加工信号相结合，用于酵母中的分泌和分泌。可以在营养培养基中以增加的产量获得产品。细胞系AB103（PYins1）保藏在A.T.C.C. 1983年4月6日，加拿大号为20,670。

2. 发明授权

US5015575A Hybrid DNA synthesis of insulin 失效
标题翻译：胰岛素的杂合DNA合成
公开(公告)号：US5015575A
公开(公告)日：1991-05-14
申请号：US479331
申请日：1990-02-13
申请人： Anthony J. Brake , Lawrence S. Cousens , Mickey S. Urdea , Pablo D. T. Valenzuela
发明人： Anthony J. Brake , Lawrence S. Cousens , Mickey S. Urdea , Pablo D. T. Valenzuela
IPC分类号： C07K14/62 , C12N15/17 , C12N15/62 , C12N15/81
CPC分类号： C07K14/62 , C12N15/625 , C12N15/81 , C07K2319/02 , C07K2319/036 , C07K2319/75
摘要： Methods and compositions are provided for efficient production of polypeptides having insulin activity. The proinsulin gene is joined to secretion and processing signals for expression and secretion in yeast. The product may be obtained in enhanced yield in the nutrient medium.Cell line pyinse was deposited at the A.T.C.C. on Apr. 6, 1983 and given Accession No. 20670.
摘要翻译：提供了方法和组合物用于有效生产具有胰岛素活性的多肽。胰岛素原基因与酵母中的分泌和加工信号相互结合，用于表达和分泌。可以在营养培养基中以增加的产量获得产品。细胞系的漂白剂沉积在A.T.C.C. 1983年4月6日，加拿大号20670。

3. 发明授权

US5612041A Recombinant herpes simplex gD vaccine 失效
标题翻译：重组单纯疱疹病毒gD疫苗
公开(公告)号：US5612041A
公开(公告)日：1997-03-18
申请号：US312666
申请日：1994-09-27
申请人： Rae L. Burke , Mickey S. Urdea , Pablo D. T. Valenzuela
发明人： Rae L. Burke , Mickey S. Urdea , Pablo D. T. Valenzuela
IPC分类号： A61K39/00 , C07K14/035 , A61K39/245
CPC分类号： C07K14/005 , A61K39/00 , C12N2710/16622
摘要： Vaccines against Herpes Simplex virus containing recombinant polypeptides which are cross-reactive with glycoprotein D of the virus, methods for their production using recombinant DNA techniques in yeast, and methods for the use of the vaccine are provided. E. coli strains HB101 containing plasmids pYHS 109 and pYHS118 were deposited at the American Type Culture Collection on Jul. 11, 1984, and granted accession nos. 39762 and 39763, respectively.
摘要翻译：针对疱疹的疫苗含有与病毒的糖蛋白D交叉反应的重组多肽的单克隆病毒，使用酵母中重组DNA技术生产的方法以及使用该疫苗的方法。含有质粒pYHS 109和pYHS118的大肠杆菌菌株HB101于1984年7月11日保藏在美国典型培养物保藏中心，并授予登记号。 39762和39763。

4. 发明授权

US4618578A Expression of glycoprotein D of herpes simplex virus 失效
标题翻译：单纯疱疹病毒糖蛋白D的表达
公开(公告)号：US4618578A
公开(公告)日：1986-10-21
申请号：US631669
申请日：1984-07-17
申请人： Rae L. Burke , Mickey S. Urdea , Pablo D. T. Valenzuela
发明人： Rae L. Burke , Mickey S. Urdea , Pablo D. T. Valenzuela
IPC分类号： A61K39/00 , A61K39/245 , C07K14/035 , C12N15/81 , C12P21/00 , C07H21/04 , C12N1/00 , C12N15/00
CPC分类号： C12N15/81 , A61K39/12 , A61K39/245 , C07K14/005 , A61K39/00 , C12N2710/16622 , C12N2710/16634 , Y10S930/224
摘要： Methods and compositions are provided for the efficient production in yeast of polypeptides which are immunologically cross-reactive with glycoprotein D of the herpes simplex virus. Synthetic DNA fragments encoding for a portion of the glycoprotein, and the naturally-occurring gene encoding for the glycoprotein and portions thereof, are expressed on plasmids in yeast. Secretion may be provided by including a secretory leader and signal processing sequence derived from the .alpha.-factor gene. Alternatively, the genes may be expressed intracellularly under the transcriptional control of a promoter derived from a gene in the yeast glycolytic pathway.E. coli strains HB101 containing plasmids pYHS109 and pYHS118 were deposited at the American Type Culture Collection on July 11, 1984, and granted accession nos. 39762 and 39763, respectively.
摘要翻译：提供了与单纯疱疹病毒的糖蛋白D免疫交叉反应的多肽的酵母中有效生产的方法和组合物。编码一部分糖蛋白的合成DNA片段和编码糖蛋白及其部分的天然存在的基因在酵母中的质粒上表达。可以通过包括来自α因子基因的分泌前导序列和信号处理序列来提供分泌。或者，基因可以在酵母糖酵解途径中从基因的启动子的转录控制下在细胞内表达。含有质粒pYHS109和pYHS118的大肠杆菌菌株HB101于1984年7月11日保藏在美国典型培养物保藏中心，并授予加入号。 39762和39763。

5. 发明授权

US4510245A Adenovirus promoter system 失效
标题翻译：腺病毒启动子系统
公开(公告)号：US4510245A
公开(公告)日：1985-04-09
申请号：US442687
申请日：1982-11-18
申请人： Lawrence S. Cousens , Graeme I. Bell , Pablo D. T. Valenzuela
发明人： Lawrence S. Cousens , Graeme I. Bell , Pablo D. T. Valenzuela
IPC分类号： C07K14/02 , C12N15/81 , C12N15/85 , C12N15/00 , C07H21/04 , C12N1/00 , C12N1/16 , C12N1/18 , C12N1/20 , C12P19/34 , C12P21/00 , C12P21/02
CPC分类号： C07K14/005 , C12N15/81 , C12N15/85 , C12N2730/10122
摘要： The adenovirus major late promoter is employed as a promoter for expression in a yeast host. Constructions are provided for expression in yeast with the adenovirus major late promoter and a coding segment.
摘要翻译：腺病毒主要晚期启动子用作在酵母宿主中表达的启动子。提供了用于在具有腺病毒主要晚期启动子和编码区段的酵母中表达的构建体。

6. 发明授权

US4876197A Eukaryotic regulatable transcription 失效
标题翻译：真核调控转录
公开(公告)号：US4876197A
公开(公告)日：1989-10-24
申请号：US760197
申请日：1985-07-29
申请人： Rae Lyn Burke , Steven Rosenberg , Jeffrey R. Shuster , Patricia A. Tekamp-Olson , Pablo D. T. Valenzuela
发明人： Rae Lyn Burke , Steven Rosenberg , Jeffrey R. Shuster , Patricia A. Tekamp-Olson , Pablo D. T. Valenzuela
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 microorganisms, 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 natrual peptide, a fused peptide, or a peptide precursor.
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。可以提供结构，其中结构基因可以在盒的读框中引入以提供天然肽，融合肽或肽前体的表达。

7. 发明授权

US06544757B1 Synthesis of human virus antigens by yeast 失效
标题翻译：通过酵母合成人类病毒抗原
公开(公告)号：US06544757B1
公开(公告)日：2003-04-08
申请号：US07209504
申请日：1988-06-21
申请人： William J. Rutter , Pablo D. T. Valenzuela , Benjamin D. Hall , Gustav Ammerer
发明人： William J. Rutter , Pablo D. T. Valenzuela , Benjamin D. Hall , Gustav Ammerer
IPC分类号： C12P2106
CPC分类号： C07K14/005 , A61K39/00 , C12N15/81 , C12N2730/10122 , Y10S530/806 , Y10S530/824 , Y10S530/826
摘要： The present invention relates to synthesis of HBSAg in yeast. Yeast expression vectors comprising a yeast promoter, ADH1, have been constructed. The region of the HBV genome coding for the S-protein, excluding a possible 163 amino acid presequence, has been transferred to the yeast expression vector. Using the described yeast vector, the successful synthesis of HBSAg by yeast has been achieved. The product is antigenic (reactive with anti-HBSAg), and a substantial portion is found associated with particles identical in electron microscopic appearance to those found in the serum of HBV-infected patients and in Alexander cells but having a smaller particle size diameter. The HBSAg synthesized by yeast has identical sedimentation behavior to purified, naturally occurring HBSAg particles purified from Alexander cells as measured by sucrose gradient sedimentation. The present invention demonstrates synthesis and assembly of a higher ordered multi-component structure resulting from expression of a heterologous DNA coding segment in a microorganism.
摘要翻译：本发明涉及酵母中HBSAg的合成。已经构建了包含酵母启动子ADH1的酵母表达载体。编码S蛋白的HBV基因组区域（不包括可能的163个氨基酸的前序列）已被转移到酵母表达载体中。使用描述的酵母载体，已经实现了酵母成功合成HBSAg。该产物具有抗原性（与抗HBSAg反应），并且发现大部分与电子显微镜外观相同的颗粒与HBV感染患者和亚历山大细胞血清中发现的颗粒相关，但具有较小的粒径直径。由酵母合成的HBSAg与通过蔗糖梯度沉降测量的从亚历山大细胞纯化的天然存在的HBSAg颗粒具有相同的沉淀行为。本发明证明了通过在微生物中表达异源DNA编码区而产生的更有序的多组分结构的合成和装配。

8. 发明授权

US5098704A Hepatitis surface antigen particle vaccine 失效
标题翻译：肝炎表面抗原颗粒疫苗
公开(公告)号：US5098704A
公开(公告)日：1992-03-24
申请号：US266795
申请日：1988-11-03
申请人： Pablo D. T. Valenzuela
发明人： Pablo D. T. Valenzuela
IPC分类号： A61K39/00 , C07K14/02 , C12N15/81
CPC分类号： C07K14/005 , C12N15/81 , A61K39/00 , C12N2730/10122
摘要： Vaccines are provided produced by hybrid DNA technology for Hepatitis B virus comprising Hepatitis B surface antigen particles containing a human polyalbumin binding site receptor. Constructs are provided for expression of the vaccine protein, which upon transformation in an appropriate host results in the production of particles useful as vaccines.
摘要翻译：通过用于乙型肝炎病毒的混合DNA技术提供的疫苗包含含有人多聚白蛋白结合位点受体的乙型肝炎表面抗原颗粒。提供用于表达疫苗蛋白质的构建体，其在合适的宿主中转化后导致可用作疫苗的颗粒的产生。

9. 发明授权

US4769238A Synthesis of human virus antigens by yeast 失效
标题翻译：通过酵母合成人类病毒抗原
公开(公告)号：US4769238A
公开(公告)日：1988-09-06
申请号：US821146
申请日：1985-12-12
申请人： William J. Rutter , Pablo D. T. Valenzuela , Benjamin D. Hall , Gustav Ammerer
发明人： William J. Rutter , Pablo D. T. Valenzuela , Benjamin D. Hall , Gustav Ammerer
IPC分类号： A61K39/00 , C07K14/02 , C12N15/81 , A61K39/29 , C12N1/18 , C12N15/00 , C12P21/02
CPC分类号： C07K14/005 , C12N15/81 , A61K39/00 , C12N2730/10122 , Y10S530/806 , Y10S530/824 , Y10S530/826
摘要： The present invention relates to synthesis of HBsAg in yeast. Yeast expression vectors comprising a yeast promoter, ADHl, have been constructed. The region of the HBV genome coding for the S-protein, excluding a possible 163 amino acid presequence, has been transferred to the yeast expression vector.Using the described yeast vector, the successful synthesis of HBsAg by yeast has been achieved. The product is antigenic (reactive with anti-HBsAg), and a substantial portion is found associated with particles identical in electron microscopic appearance to those found in the serum of HBV-infected patients and in Alexander cells but having a smaller particle size diameter. The HBsAg synthesized by yeast has identical sedimentation behavior to purified, naturally-occurring HBsAg particles purified from Alexander cells as measured by sucrose gradient sedimentation. The present invention demonstrates synthesis and assembly of a higher ordered multi-component structure resulting from expression of a heterologous DNA coding segment in a microorganism.
摘要翻译：本发明涉及酵母中HBsAg的合成。已经构建了包含酵母启动子ADH1的酵母表达载体。编码S蛋白的HBV基因组区域（不包括可能的163个氨基酸的前序列）已被转移到酵母表达载体中。使用描述的酵母载体，已经实现了通过酵母成功合成HBsAg。该产物具有抗原性（与抗HBsAg反应），并且发现大部分与电子显微镜外观相同的颗粒与HBV感染患者和亚历山大细胞血清中发现的颗粒相关，但具有较小的粒径直径。由酵母合成的HBsAg与通过蔗糖梯度沉降测量的从亚历山大细胞纯化的天然存在的HBsAg颗粒具有相同的沉淀行为。本发明证明了通过在微生物中表达异源DNA编码区而产生的更有序的多组分结构的合成和装配。

10. 发明授权

US4722840A Hybrid particle immunogens 失效
标题翻译：杂交颗粒免疫原
公开(公告)号：US4722840A
公开(公告)日：1988-02-02
申请号：US777976
申请日：1985-09-19
申请人： Pablo D. T. Valenzuela , George Kuo , Philip J. Barr
发明人： Pablo D. T. Valenzuela , George Kuo , Philip J. Barr
IPC分类号： A61K39/015 , A61K39/245 , A61K39/29 , A61K39/385 , A61P37/04 , C07K14/02 , C07K14/035 , C07K14/445 , C12N15/32 , C12N15/33 , C12N15/62 , C12N15/81 , A61K39/00 , C07K15/00 , C07K7/10 , C12P21/00
CPC分类号： C07K14/005 , A61K39/015 , A61K39/12 , A61K39/245 , A61K39/385 , C07K14/445 , C12N15/62 , C12N15/81 , A61K2039/6075 , C07K2319/00 , C07K2319/40 , C07K2319/735 , C12N2710/16622 , C12N2710/16634 , C12N2710/16722 , C12N2730/10122 , Y10S930/223 , Y10S930/31
摘要： Novel immunogenic compositions are provided involving viral particles composed at least in part of hybrid proteins of at least a portion of a particle forming protein and one or more polypeptides having at least one epitope of interest. Nucleic acid sequences are employed coding for the hybrid protein which are introduced into a host cell for expression, either by themselves or in combination with other DNA sequences coding for particle forming proteins. Expression of the DNA sequences results in formation of particles which may be isolated and used as immunogens for production of antibodies for diagnostics purposes, passive immunization, vaccination, or other uses.Saccharomyces carlsbergensis, 2150-2-3 (pDC103), was deposited on Sept. 7, 1984, at the ATCC and given ATCC Accession No. 20726. Also, Saccharomyces cerevisiae PO17 (pC1/1-MCS29) was deposited at the ATCC on Sept. 5, 1985, and given ATCC Accession No. 20770.
摘要翻译：提供了新的免疫原性组合物，其涉及至少部分由至少一部分形成颗粒的蛋白和一种或多种具有至少一种感兴趣表位的多肽的杂交蛋白质组成的病毒颗粒。编码杂交蛋白的核酸序列被引入到宿主细胞中以表达，或者通过本身或与编码颗粒形成蛋白的其他DNA序列组合。 DNA序列的表达导致形成可被分离的颗粒，并用作生产用于诊断目的的抗体的免疫原，被动免疫接种，疫苗接种或其他用途。糖酵母，2150-2-3（pDC103），于1984年9月7日在ATCC保藏，并保藏于ATCC保藏号20726.此外，酿酒酵母PO17（pC1 / 1-MCS29）保藏于ATCC 1985年9月5日，授予ATCC保藏号20770。

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