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1. 发明授权

US07094767B2 Polynucleotide herpes virus vaccine 失效
公开(公告)号：US07094767B2
公开(公告)日：2006-08-22
申请号：US09835699
申请日：2001-04-16
申请人： Marcy E. Armstrong , Robert D. Keys , John A. Lewis , Margaret A. Liu , William L. McClements
发明人： Marcy E. Armstrong , Robert D. Keys , John A. Lewis , Margaret A. Liu , William L. McClements
IPC分类号： A61K48/00
CPC分类号： C07K14/005 , A61K2039/51 , C12N2710/16622
摘要： Genes encoding herpes simplex virus type 2 (HSV-2) proteins were cloned into eukaryotic expression vectors to express the encoded proteins in mammalian muscle cells in vivo. Animals were immunized by injection of these DNA constructs, termed polynucleotide vaccines or PNV, into their muscles. In a DNA titration, it was found that a single immunization of ≧0.5 μg of (one) PNV, gave >90% seroconversion by ten weeks post immunization. Immune antisera neutralized both HSV-2 and HSV-1 in cell culture. When animals were challenged with HSV-2, significant (p

2. 发明授权

US06534312B1 Vaccines comprising synthetic genes 失效
公开(公告)号：US06534312B1
公开(公告)日：2003-03-18
申请号：US09340798
申请日：1999-06-28
申请人： John W. Shiver , Mary Ellen Davies , Daniel C. Freed , Margaret A. Liu , Helen C. Perry
发明人： John W. Shiver , Mary Ellen Davies , Daniel C. Freed , Margaret A. Liu , Helen C. Perry
IPC分类号： C12N506
CPC分类号： C07K14/005 , A61K2039/51 , C07K2319/00 , C12N15/67 , C12N2740/16122
摘要： Synthetic polynucleotides comprising a DNA sequence encoding a peptide or protein are provided. The DNA sequence of the synthetic polynucleotides comprise codons optimized for expression in a nonhomologous host. The invention is exemplified by synthetic DNA molecules encoding HIV env as well as modifications of HIV env. The codons of the synthetic molecules include the projected host cell's preferred codons. The synthetic molecules provide preferred forms of foreign genetic material. The synthetic molecules may be used as a polynucleotide vaccine which provides immunoprophylaxis against HIV infection through neutralizing antibody and cell-mediated immunity. This invention provides polynucleotides which, when directly introduced into a vertebrate in vivo, including mammals such as primates and humans, induces the expression of encoded proteins within the animal.

3. 发明授权

US5736524A Polynucleotide tuberculosis vaccine 失效
标题翻译：多核苷酸结核疫苗
公开(公告)号：US5736524A
公开(公告)日：1998-04-07
申请号：US338992
申请日：1994-11-14
申请人： Jean Content , Kris Huygen , Margaret A. Liu , Donna Montgomery , Jeffrey Ulmer
发明人： Jean Content , Kris Huygen , Margaret A. Liu , Donna Montgomery , Jeffrey Ulmer
IPC分类号： C12N15/09 , A61K39/00 , A61K39/04 , A61K48/00 , A61P31/04 , C07K14/35 , C12N15/11 , C12N15/31 , C07H21/00 , C12N15/63 , C12N15/79
CPC分类号： A61K31/711 , C07K14/35 , A61K2039/51 , A61K39/00 , A61K48/00
摘要： Genes encoding Mycobacterium tuberculosis (M.tb) proteins were cloned into eukaryotic expression vectors to express the encoded proteins in mammalian muscle cells in vivo. Animals were immunized by injection of these DNA constructs, termed polynucleotide vaccines or PNV, into their muscles. Immune antisera was produced against M.tb antigens. Specific T-cell responses were detected in spleen cells of vaccinated mice and the profile of cytokine secretion in response to antigen 85 was indicative of a T.sub.h 1 type of helper T-cell response (i.e., high IL-2 and IFN-.gamma.). Protective efficacy of an M.tb DNA vaccine was demonstrated in mice after challenge with M. bovis BCG, as measured by a reduction in mycobacterial multiplication in the spleens and lungs of M.tb DNA-vaccinated mice compared to control DNA-vaccinated mice or primary infection in naive mice.
摘要翻译：将编码结核分枝杆菌（M.tb）蛋白的基因克隆到真核表达载体中以在体内表达哺乳动物肌肉细胞中编码的蛋白质。通过将这些DNA构建体（称为多核苷酸疫苗或PNV）注入其肌肉来免疫动物。针对M.tb抗原产生免疫抗血清。在接种疫苗的小鼠的脾细胞中检测到特异性T细胞应答，响应于抗原85的细胞因子分泌曲线表示Th1型辅助T细胞应答（即高IL-2和IFN-γ）。在用牛分枝杆菌BCG攻击后的小鼠中证明了M.tb DNA疫苗的保护效力，如通过与对照DNA接种的小鼠相比，在M.tb DNA接种的小鼠的脾和肺中的分枝杆菌增殖减少所测量的幼稚小鼠初次感染。

4. 发明授权

US06995008B1 Coordinate in vivo gene expression 失效
标题翻译：协调体内基因表达
公开(公告)号：US06995008B1
公开(公告)日：2006-02-07
申请号：US09393803
申请日：1999-09-10
申请人： Margaret A. Liu , John W. Shiver , Helen C. Perry
发明人： Margaret A. Liu , John W. Shiver , Helen C. Perry
IPC分类号： C12N15/63 , C12N15/64 , C12N15/85 , C12N15/867
CPC分类号： A61K39/21 , A61K39/12 , A61K39/39 , A61K2039/53 , A61K2039/55522 , C07K14/005 , C12N15/85 , C12N2740/15022 , C12N2740/15034 , C12N2740/16122 , C12N2740/16134 , C12N2740/16222 , C12N2740/16234 , C12N2740/16322 , C12N2740/16334 , C12N2840/203
摘要： Nucleic acids, including DNA constructs and RNA transcripts, capable of inducing coordinate expression of two to three cistrons upon direct introduction into animal tissues, are bi- or tri-cistronic polynucleotides of this invention include those encoding and co-expressing HIV gene products, genes encoding antigens unrelated to HIV, and immunostimulatory gene products, including but not limited to GM-CSF, interleukins, interferon and members of the B7 family of proteins which act as T-cell costimulatory elements. The methods and polynucleotides of this invention are generally applicable to co-ordinate expression in vivo of any two or more genes in a single cell.
摘要翻译：本发明的双或三顺反子多核苷酸包括编码和共表达HIV基因产物的基因，包括编码和共表达HIV基因产物的基因，包括编码和共表达HIV基因产物的基因，包括DNA构建体和RNA转录物，能够在直接引入动物组织中诱导2至3个顺反子的配位表达编码与HIV无关的抗原，以及免疫刺激基因产物，包括但不限于作为T细胞共刺激因子的蛋白质的B7家族的GM-CSF，白介素，干扰素和成员。本发明的方法和多核苷酸通常可用于在单个细胞中统计任何两个或更多个基因的体内表达。

5. 发明授权

US06696291B2 Synthetic HIV gag genes 失效
公开(公告)号：US06696291B2
公开(公告)日：2004-02-24
申请号：US09974702
申请日：2001-10-09
申请人： John W. Shiver , Daniel C. Freed , Mary Ellen Davies , Margaret A. Liu , Helen C. Perry
发明人： John W. Shiver , Daniel C. Freed , Mary Ellen Davies , Margaret A. Liu , Helen C. Perry
IPC分类号： C12N506
CPC分类号： C07K14/005 , A61K39/00 , C07K2319/02 , C12N2740/16222 , Y02A50/412
摘要： Synthetic DNA molecules encoding HIV gag and modifications of HIV gag are provided. The codons of the synthetic molecules are codons preferred by the projected host cell. The synthetic molecules may be used as a polynucleotide vaccine which provides effective immunoprophylaxis against HIV infection through stimulation of neutralizing antibody and cell-mediated immunity.

6. 发明授权

US06653125B2 Synthetic hepatitis C genes 失效
标题翻译：合成丙型肝炎基因
公开(公告)号：US06653125B2
公开(公告)日：2003-11-25
申请号：US09194949
申请日：2000-02-17
申请人： John J. Donnelly , Margaret A. Liu , John W. Shiver , Tong-Ming Fu
发明人： John J. Donnelly , Margaret A. Liu , John W. Shiver , Tong-Ming Fu
IPC分类号： C12N1579
CPC分类号： C07K14/005 , A61K39/00 , A61K48/00 , A61K2039/53 , C12N2770/24222
摘要： The present invention relates to polynucleotides comprising a DNA sequence encoding an HCV protein and fragments thereof that contain codons optimized for expression in a vertebrate host. Uses of the polynucleotides include eliciting an immune response specifically recognizing HCV.
摘要翻译：本发明涉及包含编码HCV蛋白的DNA序列的多核苷酸及其片段，其含有在脊椎动物宿主中表达的优化的密码子。多核苷酸的用途包括引发特异性识别HCV的免疫应答。

7. 发明授权

US06384018B1 Polynucleotide tuberculosis vaccine 失效
标题翻译：多核苷酸结核疫苗
公开(公告)号：US06384018B1
公开(公告)日：2002-05-07
申请号：US09010733
申请日：1998-01-22
申请人： Jean Content , Kris Huygen , Margaret A. Liu , Donna Montgomery , Jeffrey Ulmer
发明人： Jean Content , Kris Huygen , Margaret A. Liu , Donna Montgomery , Jeffrey Ulmer
IPC分类号： A01N4304
CPC分类号： A61K31/711 , A61K39/00 , A61K48/00 , A61K2039/51 , C07K14/35
摘要： Genes encoding Mycobacterium tuberculosis (M.tb) proteins were cloned into eukaryotic expression vectors to express the encoded proteins in mammalian muscle cells in vivo. Animals were immunized by injection of these DNA constructs, termed polynucleotide vaccines or PNV, into their muscles. Immune antisera was produced against M.tb antigens. Specific T-cell responses were detected in spleen cells of vaccinated mice and the profile of cytokine secretion in response to antigen 85 was indicative of a Th1 type of helper T-cell response (i.e., high IL-2 and IFN-&ggr;). Protective efficacy of an M.tb DNA vaccine was demonstrated in mice after challenge with M.bovis BCG, as measured by a reduction in mycobacterial multiplication in the spleens and lungs of M.tb DNA-vaccinated mice compared to control DNA-vaccinated mice or primary infection in naive mice.
摘要翻译：将编码结核分枝杆菌（M.tb）蛋白的基因克隆到真核表达载体中以在体内表达哺乳动物肌肉细胞中编码的蛋白质。通过将这些DNA构建体（称为多核苷酸疫苗或PNV）注入其肌肉来免疫动物。针对M.tb抗原产生免疫抗血清。在接种疫苗的小鼠的脾细胞中检测到特异性T细胞应答，响应于抗原85的细胞因子分泌曲线表示Th1型辅助T细胞应答（即高IL-2和IFN-γ）。在用M.bovis BCG攻击后的小鼠中证明了M.tb DNA疫苗的保护功效，如通过与对照DNA接种的小鼠相比，在接种M.tb DNA的小鼠的脾和肺中的分枝杆菌增殖减少所测量的幼稚小鼠初次感染。

8. 发明授权

US5866553A Polynucleotide vaccine for papillomavirus 失效
标题翻译：乳头瘤病毒的多核苷酸疫苗
公开(公告)号：US5866553A
公开(公告)日：1999-02-02
申请号：US750810
申请日：1996-12-17
申请人： John J. Donnelly , Margaret A. Liu , Douglas Martinez , Donna L. Montgomery
发明人： John J. Donnelly , Margaret A. Liu , Douglas Martinez , Donna L. Montgomery
IPC分类号： C12N15/09 , A61K39/12 , A61K48/00 , A61P31/12 , A61P37/04 , C07H21/04 , C07K14/025 , C12N15/00 , C12N15/37 , C12R1/92 , A01N43/04
CPC分类号： C12N7/00 , C07K14/005 , A61K48/00 , C12N2710/20022
摘要： DNA constructs encoding papilloma virus gene products, capable of being expressed upon direct introduction into animal tissues, are novel prophylactic pharmaceuticals which can provide immune protection against infection by papilloma virus.
摘要翻译： PCT No.PCT / US95 / 06915 Sec。 371日期：1996年12月17日 102（e）日期1996年12月17日PCT归档1995年6月1日PCT公布。公开号WO96 / 00583 日期1996年1月11日编码能够直接引入动物组织中表达的乳头状瘤病毒基因产物的DNA构建体是可以提供针对乳头状瘤病毒感染的免疫保护的新型预防药物。

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