公开(公告)号：US5561064A

公开(公告)日：1996-10-01

申请号：US192151

申请日：1994-02-01

申请人： Magda Marquet ,  Nancy Horn ,  Jennifer Meek ,  Gregg Budahazi

发明人： Magda Marquet ,  Nancy Horn ,  Jennifer Meek ,  Gregg Budahazi

IPC分类号： C12N15/09 ,  C07K14/74 ,  C12N1/12 ,  C12N1/13 ,  C12N15/10 ,  C12P21/02 ,  C12R1/19 ,  C12R1/91 ,  C12N15/00

CPC分类号： C12N15/101 ,  C07K14/70539 ,  C12N15/1003

摘要： The invention relates to a method for producing plasmid DNA, comprising the steps of: (a) lysing cells containing the plasmid DNA to obtain a lysate; (b) treating the lysate by a means for removing insoluble material to obtain a solute; and (c) applying the solute to differential PEG precipitations and chromatography to purify the plasmid DNA. In other embodiments of the invention, the plasmid DNA is produced with GRAS reagents; the plasmid DNA is produced in the absence of enzymes; the plasmid DNA is produced in the absence of organic extractants; the plasmid DNA is produced in the absence of mutagens; the lysing, treating and applying steps are scalable to result in the large scale manufacture of the plasmid DNA; and the lysing, treating and applying steps result in the generation of pharmaceutical grade material.

摘要翻译： 本发明涉及一种生产质粒DNA的方法，包括以下步骤：（a）裂解含有质粒DNA的细胞以获得裂解物; （b）通过去除不溶物质的方法处理裂解物以获得溶质; 和（c）将溶质应用于差示PEG沉淀和色谱法纯化质粒DNA。 在本发明的其它实施方案中，质粒DNA用GRAS试剂制备; 在不存在酶的情况下产生质粒DNA; 在不存在有机萃取剂的情况下生产质粒DNA; 在不存在诱变剂的情况下产生质粒DNA; 裂解，处理和施用步骤是可扩展的，导致质粒DNA的大规模生产; 并且裂解，处理和施用步骤导致药物级材料的产生。

公开(公告)号：US09180162B2

公开(公告)日：2015-11-10

申请号：US14176813

申请日：2014-02-10

申请人： Vical Incorporated

发明人： Gary G. Hermanson ,  Andrew J. Geall ,  Mary Kopke Wloch

IPC分类号： C07K14/005 ,  A61K39/245 ,  A61K38/16 ,  C07H21/00 ,  A61K39/12 ,  C07K14/045 ,  A61K39/00 ,  A61K35/763

CPC分类号： A61K38/16 ,  A61K35/763 ,  A61K38/162 ,  A61K39/00 ,  A61K39/12 ,  A61K39/245 ,  A61K2039/53 ,  A61K2039/55522 ,  A61K2039/55555 ,  A61K2039/55572 ,  C07H21/00 ,  C07K14/005 ,  C07K14/045 ,  C12N2710/16122 ,  C12N2710/16134 ,  C12N2800/22

摘要： The invention is related to polynucleotide-based cytomegalovirus vaccines. In particular, the invention is plasmids operably encoding HCMV antigens, in which the naturally-occurring coding regions for the HCMV antigens have been modified for improved translation in human or other mammalian cells through codon optimization. HCMV antigens which are useful in the invention include, but are not limited to pp65, glycoprotein B (gB), IE1, and fragments, variants or derivatives of either of these antigens. In certain embodiments, sequences have been deleted, e.g., the Arg435-Lys438 putative kinase in pp65 and the membrane anchor and endocellular domains in gB. The invention is further directed to methods to induce an immune response to HCMV in a mammal, for example, a human, comprising delivering a plasmid encoding a codon-optimized HCMV antigen as described above. The invention is also directed to pharmaceutical compositions comprising plasmids encoding a codon-optimized HCMV antigen as described above, and further comprising adjuvants, excipients, or immune modulators.

摘要翻译： 本发明涉及基于多核苷酸的巨细胞病毒疫苗。 特别地，本发明是可操作地编码HCMV抗原的质粒，其中用于HCMV抗原的天然存在的编码区已被修饰以通过密码子优化改善人或其它哺乳动物细胞中的翻译。 可用于本发明的HCMV抗原包括但不限于pp65，糖蛋白B（gB），IE1以及这些抗原之一的片段，变体或衍生物。 在某些实施方案中，已经删除了序列，例如pp65中的Arg435-Lys438推定的激酶和gB中的膜锚定和内细胞域。 本发明还涉及在哺乳动物例如人中诱导对HCMV的免疫应答的方法，其包括如上所述递送编码密码子优化的HCMV抗原的质粒。 本发明还涉及包含编码如上所述的密码子优化的HCMV抗原的质粒的药物组合物，并且还包含佐剂，赋形剂或免疫调节剂。

公开(公告)号：US08828408B2

公开(公告)日：2014-09-09

申请号：US13843176

申请日：2013-03-15

申请人： The University of Washington ,  Vical Incorporated

发明人： Adrian Vilalta ,  Michal Margalith ,  Lichun Dong ,  David M. Koelle

IPC分类号： A61K39/245 ,  C07K14/005 ,  C12N15/38 ,  C12N15/00 ,  A61K39/00

CPC分类号： A61K39/245 ,  A61K39/12 ,  A61K39/39 ,  A61K2039/53 ,  A61K2039/54 ,  A61K2039/545 ,  A61K2039/55511 ,  A61K2039/55572 ,  A61K2039/57 ,  A61K2039/572 ,  A61K2039/575 ,  C07K14/005 ,  C12N7/00 ,  C12N15/117 ,  C12N2310/17 ,  C12N2320/31 ,  C12N2710/16622 ,  C12N2710/16634

摘要： This invention relates to therapeutic polynucleotide compositions and methods for systemic immune activation which are effective for eliciting both a systemic, non-antigen specific immune response and a strong antigen-specific immune response in mammals. The polynucleotide compositions are particularly effective for protecting mammals from herpes simplex virus (HSV), such as HSV VP13/14 polypeptides.

摘要翻译： 本发明涉及用于全身免疫活化的治疗性多核苷酸组合物和方法，其有效引发哺乳动物的全身性，非抗原特异性免疫应答和强抗原特异性免疫应答。 多核苷酸组合物特别有效地保护哺乳动物免于单纯疱疹病毒（HSV），如HSV VP13 / 14多肽。

公开(公告)号：US20130273078A1

公开(公告)日：2013-10-17

申请号：US13830543

申请日：2013-03-14

申请人： Vical Incorporated

发明人： Alain P. ROLLAND ,  John Doukas ,  Dmitri Kharkevitch

IPC分类号： A61K39/395 ,  A61K31/7088

CPC分类号： A61K39/3955 ,  A61K31/7088 ,  A61K39/00 ,  A61K39/39558 ,  A61K45/06 ,  C07K16/2818 ,  A61K2300/00

摘要： The present disclosure provides combinations of immunotherapeutics and methods for treating medical conditions that are characterized by the lack of an effective immune response, for example as would result following a down-regulation of MHC class I, such as in cancer. The immunotherapeutic compositions of the invention, which can be used to treat the medical conditions, include one or more immunostimulatory antibodies or molecules having specificity for CTLA-4, PD-1, PD-L1, PD-L2, CD40, OX40, CD137, GITR, ILT2, or ILT3, or ligands for these molecules (e.g., an isolated fully-human monoclonal antibody) in association with one or more alloantigens, such as, vector(s) capable of expressing protein(s) or peptide(s) that stimulate T-cell immunity against tissues or cells, formulated in a pharmaceutically acceptable carrier. The proteins or peptides may comprise class I major histocompatibility complex (MHC) antigens, β2-microglobulins, or cytokines. The MHC antigen may be foreign to the subject. The MHC antigen may be HLA-B7.

公开(公告)号：US08541628B2

公开(公告)日：2013-09-24

申请号：US10748853

申请日：2003-12-30

申请人： Carl J Wheeler

发明人： Carl J Wheeler

IPC分类号： C07C43/00 ,  C07C205/00 ,  A61K38/00 ,  A61K48/00 ,  A61K31/08 ,  A61K31/04 ,  A01N31/14 ,  A01N33/18 ,  A01N33/24

CPC分类号： C07K5/0825 ,  A61K9/1272 ,  A61K47/54 ,  A61K47/543 ,  C07C225/06 ,  C07C229/12 ,  C07C237/06 ,  C07C271/12 ,  C07C275/14 ,  C07C279/36 ,  C07C323/59 ,  C07K5/081

摘要： Cationic lipids having a derivatized quaternary ammonium head group that provide improved cell targeting ability and enhanced transfective efficacy for introducing molecules into cells are provided.

摘要翻译： 提供具有衍生的季铵头基的阳离子脂质，其提供改善的细胞靶向能力和增强的将细胞分子引入细胞的转染效能。

公开(公告)号：US20130071403A1

公开(公告)日：2013-03-21

申请号：US13622210

申请日：2012-09-18

申请人： Vical Incorporated

发明人： Alain P. ROLLAND ,  John Doukas ,  Dmitri Kharkevitch

IPC分类号： A61K39/395 ,  A61P35/04 ,  A61P35/00

CPC分类号： A61K39/3955 ,  A61K31/7088 ,  A61K39/00 ,  A61K39/39558 ,  A61K45/06 ,  C07K16/2818 ,  A61K2300/00

摘要： The present disclosure provides combinations of immunotherapeutics and methods for treating medical conditions that are characterized by the lack of an effective immune response, for example as would result following a down-regulation of MHC class I, such as in cancer. The immunotherapeutic compositions of the invention, which can be used to treat the medical conditions, include one or more immunostimulatory antibodies or molecules having specificity for CTLA-4, PD-1, PD-L1, PD-L2, CD40, OX40, CD137, GITR, ILT2, or ILT3, or ligands for these molecules (e.g., an isolated fully-human monoclonal antibody) in association with one or more alloantigens, such as, vector(s) capable of expressing protein(s) or peptide(s) that stimulate T-cell immunity against tissues or cells, formulated in a pharmaceutically acceptable carrier. The proteins or peptides may comprise class I major histocompatibility complex (MHC) antigens, β2-microglobulins, or cytokines. The MHC antigen may be foreign to the subject. The MHC antigen may be HLA-B7.

摘要翻译： 本公开提供了免疫治疗剂和用于治疗医学病症的方法的组合，其特征在于缺乏有效的免疫应答，例如在MHC I类的下调（例如癌症）后将导致的。 可用于治疗医学病症的本发明的免疫治疗组合物包括一种或多种针对CTLA-4，PD-1，PD-L1，PD-L2，CD40，OX40，CD137等具有特异性的免疫刺激性抗体或分子。 GITR，ILT2或ILT3或这些分子的配体（例如，分离的完全人单克隆抗体）与一种或多种同种异体抗原（例如能够表达蛋白质或肽）的载体结合， 其刺激配制在药学上可接受的载体中的针对组织或细胞的T细胞免疫。 蛋白质或肽可以包含I类主要组织相容性复合体（MHC）抗原，2-微球蛋白或细胞因子。 MHC抗原对受试者可能是外来的。 MHC抗原可以是HLA-B7。

公开(公告)号：US20120328657A1

公开(公告)日：2012-12-27

申请号：US13585668

申请日：2012-08-14

申请人： Adrian VILALTA ,  Michal Margalith ,  Lichun Dong ,  David M. Koelle

发明人： Adrian VILALTA ,  Michal Margalith ,  Lichun Dong ,  David M. Koelle

IPC分类号： A61K39/245 ,  A61P31/22 ,  C07K14/035 ,  C12N15/38 ,  C12N15/62

CPC分类号： A61K39/245 ,  A61K39/12 ,  A61K39/39 ,  A61K2039/53 ,  A61K2039/54 ,  A61K2039/545 ,  A61K2039/55511 ,  A61K2039/55572 ,  A61K2039/57 ,  A61K2039/572 ,  A61K2039/575 ,  C07K14/005 ,  C12N7/00 ,  C12N15/117 ,  C12N2310/17 ,  C12N2320/31 ,  C12N2710/16622 ,  C12N2710/16634

摘要： This invention relates to a method for systemic immune activation which is effective for eliciting both a systemic, non-antigen specific immune response and a strong antigen-specific immune response in a mammal. The method is particularly effective for protecting a mammal from herpes simplex virus. Also disclosed are therapeutic compositions useful in such a method.

公开(公告)号：US20110177124A1

公开(公告)日：2011-07-21

申请号：US13013752

申请日：2011-01-25

申请人： Gary G. HERMANSON ,  Andrew J. Geall ,  Mary Kopke Wloch

发明人： Gary G. HERMANSON ,  Andrew J. Geall ,  Mary Kopke Wloch

IPC分类号： A61K39/245 ,  C07H21/04 ,  C12N15/63 ,  C12N7/04 ,  C07K14/045 ,  A61P31/22 ,  A61P37/04

CPC分类号： A61K38/16 ,  A61K35/763 ,  A61K38/162 ,  A61K39/00 ,  A61K39/12 ,  A61K39/245 ,  A61K2039/53 ,  A61K2039/55522 ,  A61K2039/55555 ,  A61K2039/55572 ,  C07H21/00 ,  C07K14/005 ,  C07K14/045 ,  C12N2710/16122 ,  C12N2710/16134 ,  C12N2800/22

摘要： The invention is related to polynucleotide-based cytomegalovirus vaccines. In particular, the invention is plasmids operably encoding HCMV antigens, in which the naturally-occurring coding regions for the HCMV antigens have been modified for improved translation in human or other mammalian cells through codon optimization. HCMV antigens which are useful in the invention include, but are not limited to pp65, glycoprotein B (gB), IE1, and fragments, variants or derivatives of either of these antigens. In certain embodiments, sequences have been deleted, e.g., the Arg435-Lys438 putative kinase in pp65 and the membrane anchor and endocellular domains in gB. The invention is further directed to methods to induce an immune response to HCMV in a mammal, for example, a human, comprising delivering a plasmid encoding a codon-optimized HCMV antigen as described above. The invention is also directed to pharmaceutical compositions comprising plasmids encoding a codon-optimized HCMV antigen as described above, and further comprising adjuvants, excipients, or immune modulators.

摘要翻译： 本发明涉及基于多核苷酸的巨细胞病毒疫苗。 特别地，本发明是可操作地编码HCMV抗原的质粒，其中用于HCMV抗原的天然存在的编码区已通过密码子优化被修饰以改善人或其他哺乳动物细胞中的翻译。 可用于本发明的HCMV抗原包括但不限于pp65，糖蛋白B（gB），IE1以及这些抗原之一的片段，变体或衍生物。 在某些实施方案中，已经删除了序列，例如pp65中的Arg435-Lys438推定的激酶和gB中的膜锚定和内细胞域。 本发明还涉及在哺乳动物例如人中诱导对HCMV的免疫应答的方法，其包括如上所述递送编码密码子优化的HCMV抗原的质粒。 本发明还涉及包含编码如上所述的密码子优化的HCMV抗原的质粒的药物组合物，并且还包含佐剂，赋形剂或免疫调节剂。

公开(公告)号：US20110081686A1

公开(公告)日：2011-04-07

申请号：US12895441

申请日：2010-09-30

申请人： C. Marston MANTHORPE ,  Mark E. MINICK ,  Edward M. DOMANICO

发明人： C. Marston MANTHORPE ,  Mark E. MINICK ,  Edward M. DOMANICO

IPC分类号： C12P19/34 ,  C12M1/38 ,  C12M1/00

CPC分类号： B01L7/525 ,  B01L2300/1838

摘要： A reactor and methods of use are disclosed for amplification of an amplicon. The reactor includes a housing having a fluid path with a fluid inlet and a fluid outlet and one or more reaction chambers suitable for housing the amplicon. The reaction chambers are positioned within the housing in thermal communication with a fluid flowing in the fluid path to heat and/or cool the reaction chambers and the inside of the reaction chambers are coated with or are a plastic material. A variable temperature fluid source is in fluid communication with the fluid inlet and the fluid source is configured to provide fluid at temperatures suitable for amplification, including a denature temperature, an anneal temperature, and an extension temperature. A controller is coupled to the variable temperature fluid source to control a fluid temperature within the fluid path by controlling the variable temperature fluid source.

摘要翻译： 公开了一种反应器和使用方法用于扩增扩增子。 反应器包括具有流体路径的壳体，其具有流体入口和流体出口以及适于容纳扩增子的一个或多个反应室。 反应室位于壳体内，与在流体路径中流动的流体热连通以加热和/或冷却反应室，并且反应室的内部涂覆有塑料材料或塑料材料。 可变温度流体源与流体入口流体连通，并且流体源构造成在适于放大的温度下提供流体，包括变性温度，退火温度和延伸温度。 控制器耦合到可变温度流体源，以通过控制可变温度流体源来控制流体路径内的流体温度。

公开(公告)号：US20100273254A1

公开(公告)日：2010-10-28

申请号：US12773780

申请日：2010-05-04

申请人： Gregg BUDAHAZI ,  Blake Goff

发明人： Gregg BUDAHAZI ,  Blake Goff

IPC分类号： C12N15/74

CPC分类号： C12N15/1017 ,  C12N15/101

摘要： The invention relates to a process for purifying plasmid DNA. The invention also relates to a DNA product made by the process of the invention. The DNA product is suitable for pharmaceutical use.

摘要翻译： 本发明涉及一种纯化质粒DNA的方法。 本发明还涉及通过本发明的方法制备的DNA产物。 该DNA产品适用于药物使用。