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    Enhanced first generation adenovirus vaccines expressing codon optimized HIV1-Gag, Pol, Nef and modifications
    2.
    发明申请
    Enhanced first generation adenovirus vaccines expressing codon optimized HIV1-Gag, Pol, Nef and modifications 审中-公开
    表达密码子优化的HIV1-Gag，Pol，Nef和修饰的增强的第一代腺病毒疫苗

    公开(公告)号：US20070054395A1

    公开(公告)日：2007-03-08

    申请号：US11599584

    申请日：2006-11-13

    申请人： Emilio Emini ,  Rima Youil ,  Andrew Bett ,  Ling Chen ,  David Kaslow ,  John Shiver ,  Timothy Toner ,  Danilo Casimiro

    发明人： Emilio Emini ,  Rima Youil ,  Andrew Bett ,  Ling Chen ,  David Kaslow ,  John Shiver ,  Timothy Toner ,  Danilo Casimiro

    IPC分类号： C12Q1/68 ,  C12N15/00

    CPC分类号： C12N15/86 ,  A61K39/12 ,  A61K39/21 ,  A61K2039/5256 ,  A61K2039/53 ,  A61K2039/545 ,  A61K2039/55555 ,  A61K2039/57 ,  C07K14/005 ,  C12N7/00 ,  C12N15/63 ,  C12N2710/10343 ,  C12N2710/10351 ,  C12N2740/16122 ,  C12N2740/16134 ,  C12N2740/16222 ,  C12N2740/16234 ,  C12N2740/16322 ,  C12N2740/16334 ,  C12N2830/42

    摘要： First generation adenoviral vectors and associated recombinant adenovirus-based HIV vaccines which show enhanced stability and growth properties and greater cellular-mediated immunity are described within this specification. These adenoviral vectors are utilized to generate and produce through cell culture various adenoviral-based HIV-1 vaccines which contain HIV-1 gag, HIV-1 pol and/or HIV-1 nef polynucleotide pharmaceutical products, and biologically relevant modifications thereof. These adenovirus vaccines, when directly introduced into living vertebrate tissue, preferably a mammalian host such as a human or a non-human mammal of commercial or domestic veterinary importance, express the HIV1-Gag, Pol and/or Nef protein or biologically modification thereof, inducing a cellular immune response which specifically recognizes HIV-1. The exemplified polynucleotides of the present invention are synthetic DNA molecules encoding HIV-1 Gag, encoding codon optimized HIV-1 Pol, derivatives of optimized HIV-1 Pol (including constructs wherein protease, reverse transcriptase, RNAse H and integrase activity of HIV-1 Pol is inactivated), HIV-1 Nef and derivatives of optimized HIV-1 Nef, including nef mutants which effect wild type characteristics of Nef, such as myristylation and down regulation of host CD4. The adenoviral vaccines of the present invention, when administered alone or in a combined modality regime, will offer a prophylactic advantage to previously uninfected individuals and/or provide a therapeutic effect by reducing viral load levels within an infected individual, thus prolonging the asymptomatic phase of HIV-1 infection.

    摘要翻译： 在本说明书中描述了显示增强的稳定性和生长特性以及更大的细胞介导的免疫的第一代腺病毒载体和相关重组腺病毒的HIV疫苗。 这些腺病毒载体用于通过细胞培养产生和产生各种含有HIV-1 gag，HIV-1 pol和/或HIV-1 nef多核苷酸药物产品的基于腺病毒的HIV-1疫苗及其生物相关的修饰。 这些腺病毒疫苗当直接引入活的脊椎动物组织中时，优选哺乳动物宿主例如具有商业或家庭兽医重要性的人或非人哺乳动物，表达HIV1-Gag，Pol和/或Nef蛋白或其生物修饰， 诱导特异性识别HIV-1的细胞免疫应答。 本发明的示例性多核苷酸是编码HIV-1Gag的编码密码子优化的HIV-1 Pol的合成DNA分子，其优化的HIV-1 Pol的衍生物（包括其中蛋白酶，逆转录酶，RNAse H和HIV-1的整合酶活性 Pol被灭活），HIV-1 Nef和优化的HIV-1 Nef的衍生物，包括影响Nef野生型特征的nef突变体，如主体CD4的肉豆蔻酰化和下调。 本发明的腺病毒疫苗当单独施用或以组合的方式给药时，将对先前未感染的个体提供预防优势，和/或通过减少被感染个体内的病毒载量水平提供治疗效果，从而延长无症状期 HIV-1感染。

    Enhanced first generation adenovirus vaccines expressing codon optimized HIV1-Gag, Pol, Nef and modifications
    3.
    发明申请
    Enhanced first generation adenovirus vaccines expressing codon optimized HIV1-Gag, Pol, Nef and modifications 审中-公开
    表达密码子优化的HIV1-Gag，Pol，Nef和修饰的增强的第一代腺病毒疫苗

    公开(公告)号：US20050070017A1

    公开(公告)日：2005-03-31

    申请号：US10636730

    申请日：2003-08-07

    申请人： Emilio Emini ,  Rima Youil ,  Andrew Bett ,  Ling Chen ,  David Kaslow ,  John Shiver ,  Timothy Toner ,  Danilo Casimiro

    发明人： Emilio Emini ,  Rima Youil ,  Andrew Bett ,  Ling Chen ,  David Kaslow ,  John Shiver ,  Timothy Toner ,  Danilo Casimiro

    IPC分类号： C07K14/16 ,  C12N7/01 ,  C12N7/02 ,  C12N15/861 ,  A61K39/12 ,  C12N7/00

    CPC分类号： C12N7/00 ,  A61K2039/5256 ,  A61K2039/53 ,  A61K2039/545 ,  A61K2039/57 ,  C07K14/005 ,  C12N15/86 ,  C12N2710/10343 ,  C12N2710/10351 ,  C12N2740/16122 ,  C12N2740/16134 ,  C12N2740/16322 ,  C12N2740/16334 ,  C12N2830/42

    摘要： First generation adenoviral vectors and associated recombinant adenovirus-based HIV vaccines which show enhanced stability and growth properties and greater cellular-mediated immunity are described within this specification. These adenoviral vectors are utilized to generate and produce through cell culture various adenoviral-based HIV-1 vaccines which contain HIV-1 gag, HIV-1 pol and/or HIV-1 nef polynucleotide pharmaceutical products, and biologically relevant modifications thereof. These adenovirus vaccines, when directly introduced into living vertebrate tissue, preferably a mammalian host such as a human or a non-human mammal of commercial or domestic veterinary importance, express the HIV1-Gag, Pol and/or Nef protein or biologically modification thereof, inducing a cellular immune response which specifically recognizes HIV-1. The exemplified polynucleotides of the present invention are synthetic DNA molecules encoding HIV-1 Gag, encoding codon optimized HIV-1 Pol, derivatives of optimized HIV-1 Pol (including constructs wherein protease, reverse transcriptase, RNAse H and integrase activity of HIV-1 Pol is inactivated), HIV-1 Nef and derivatives of optimized HIV-1 Nef, including nef mutants which effect wild type characteristics of Nef, such as myristylation and down regulation of host CD4. The adenoviral vaccines of the present invention, when administered alone or in a combined modality regime, will offer a prophylactic advantage to previously uninfected individuals and/or provide a therapeutic effect by reducing viral load levels within an infected individual, thus prolonging the asymptomatic phase of HIV-1 infection.

    摘要翻译： 在本说明书中描述了显示增强的稳定性和生长特性以及更大的细胞介导的免疫的第一代腺病毒载体和相关重组腺病毒的HIV疫苗。 这些腺病毒载体用于通过细胞培养产生和产生各种含有HIV-1 gag，HIV-1 pol和/或HIV-1 nef多核苷酸药物产品的基于腺病毒的HIV-1疫苗及其生物相关的修饰。 这些腺病毒疫苗当直接引入活的脊椎动物组织中时，优选哺乳动物宿主例如具有商业或家庭兽医重要性的人或非人哺乳动物，表达HIV1-Gag，Pol和/或Nef蛋白或其生物修饰， 诱导特异性识别HIV-1的细胞免疫应答。 本发明的示例性多核苷酸是编码HIV-1Gag的编码密码子优化的HIV-1 Pol的合成DNA分子，其优化的HIV-1 Pol的衍生物（包括其中蛋白酶，逆转录酶，RNAse H和HIV-1的整合酶活性 Pol被灭活），HIV-1 Nef和优化的HIV-1 Nef的衍生物，包括影响Nef野生型特征的nef突变体，如主体CD4的肉豆蔻酰化和下调。 本发明的腺病毒疫苗当单独施用或以组合的方式给药时，将对先前未感染的个体提供预防优势，和/或通过减少被感染个体内的病毒载量水平提供治疗效果，从而延长无症状期 HIV-1感染。

    Method of inducing an enhanced immune response against hiv
    4.
    发明申请
    Method of inducing an enhanced immune response against hiv 审中-公开
    诱导针对HIV的增强的免疫应答的方法

    公开(公告)号：US20060165664A1

    公开(公告)日：2006-07-27

    申请号：US10507237

    申请日：2003-03-12

    申请人： Emilio Emini ,  John Shiver ,  Danilo Casimiro ,  Andrew Bett ,  Xiaoping Liang ,  Tong-Ming Fu

    发明人： Emilio Emini ,  John Shiver ,  Danilo Casimiro ,  Andrew Bett ,  Xiaoping Liang ,  Tong-Ming Fu

    IPC分类号： A61K48/00 ,  A61K39/21

    CPC分类号： C12N15/86 ,  A61K39/12 ,  A61K39/21 ,  A61K2039/5256 ,  A61K2039/545 ,  C07K14/005 ,  C12N2710/10343 ,  C12N2740/16122 ,  C12N2740/16134 ,  C12N2740/16234 ,  C12N2740/16322 ,  C12N2740/16334 ,  C12N2830/42

    摘要： An efficient means of inducing an immune response against human immunodeficiency virus (HIV) utilizing specific prime-boost regimes is disclosed. The specific prime-boost regimes employ a heterologous prime-boost protocol employing recombinant adenoviral vectors of alternative and distinct serotypes comprising exogenous genetic material encoding a common HIV antigen. Vaccines administered into living vertebrate tissue in accordance with the disclosed regimes, preferably a mammalian host, such as a human or a non-human mammal of commercial or domestic veterinary importance, express the HIV-1 antigen (e.g., Gag), inducing a cellular immune response which specifically recognizes HIV-1. It is believed that the disclosed prime/boost regime will offer a prophylactic advantage to previously uninfected individuals and/or provide a therapeutic effect by reducing viral load levels within an infected individual, thus prolonging the asymptomatic phase of HIV-1 infection.

    摘要翻译： 公开了一种利用特定初始 - 加强方案诱导针对人类免疫缺陷病毒（HIV）的免疫应答的有效手段。 特定的初始 - 加强方案采用异源初始 - 加强方案，其使用包含编码常见HIV抗原的外源遗传物质的替代和不同血清型的重组腺病毒载体。 根据所公开的方案，优选哺乳动物宿主，如商业或家畜兽医学重要的人或非人哺乳动物施用于活的脊椎动物组织中的疫苗表达HIV-1抗原（例如，Gag），诱导细胞 特异性识别HIV-1的免疫反应。 相信所公开的主要/加强方案将对先前未感染的个体提供预防优势，和/或通过减少感染个体内的病毒载量水平提供治疗效果，从而延长HIV-1感染的无症状期。

    Adenoviral Vector Compositions
    5.
    发明申请
    Adenoviral Vector Compositions 审中-公开
    腺病毒载体组成

    公开(公告)号：US20080063656A1

    公开(公告)日：2008-03-13

    申请号：US11659671

    申请日：2005-08-05

    申请人： Emilio Emini ,  John Shiver ,  Danilo Casimiro ,  Andrew Bett

    发明人： Emilio Emini ,  John Shiver ,  Danilo Casimiro ,  Andrew Bett

    IPC分类号： A61K31/70 ,  A61K35/00 ,  A61K39/00 ,  A61P43/00 ,  C12N15/00 ,  C12N7/00

    CPC分类号： C12N15/86 ,  A61K39/12 ,  A61K39/21 ,  A61K48/00 ,  A61K48/0083 ,  A61K2039/53 ,  A61K2039/545 ,  A61K2039/57 ,  C07K14/005 ,  C12N7/00 ,  C12N2710/10343 ,  C12N2740/16134 ,  C12N2740/16334

    摘要： Applicants disclose herein novel methods, vectors, and vector compositions for improving the efficiency of adenoviral vectors in the delivery and expression of heterologous nucleic acid encoding a polypeptide(s) (e.g, a protein or antigen) of interest. Adenoviral infection is quite common in the general population, and a large percentage of people have neutralizing antibodies to the more prevalent adenoviral serotypes. Such pre-existing anti-adenoviral immunity can dampen or possibly abrogate the effectiveness of this virus for the delivery and expression of heterologous proteins or antigens. The method taught herein functions to offset pre-existing immunity through the delivery of the protein or antigen by a cocktail of at least two adenoviral serotypes. Utilizing a composition of at least two adenoviral serotypes in this manner has been found to increase the effectiveness of adenoviral administration. Adenoviral vectors of utility in the elicitation of an immune response against Human Immunodeficiency Virus (“HIV”) are also disclosed.

    摘要翻译： 申请人在此公开了新颖的方法，载体和载体组合物，用于提高编码感兴趣的多肽（例如，蛋白质或抗原）的异源核酸的递送和表达中腺病毒载体的效率。 腺病毒感染在普通人群中相当普遍，并且大部分人群对更普遍的腺病毒血清型具有中和抗体。 这种预先存在的抗腺病毒免疫可以抑制或可能地消除该病毒用于递送和表达异源蛋白质或抗原的有效性。 本文教导的方法通过至少两种腺病毒血清型的混合物通过递送蛋白质或抗原来抵消预先存在的免疫力。 已经发现以这种方式利用至少两种腺病毒血清型的组合物来增加腺病毒给药的有效性。 还公开了针对人类免疫缺陷病毒（“HIV”）免疫应答的效用的腺病毒载体。

    Polynucleotide vaccines expressing codon optimized HIV-1 Pol and modified HIV-1 Pol
    8.
    发明申请
    Polynucleotide vaccines expressing codon optimized HIV-1 Pol and modified HIV-1 Pol 审中-公开
    表达密码子优化的HIV-1 Pol和修饰的HIV-1 Pol的多核苷酸疫苗

    公开(公告)号：US20060148750A1

    公开(公告)日：2006-07-06

    申请号：US11345127

    申请日：2006-02-01

    申请人： John Shiver ,  Helen Perry ,  Danilo Casimiro ,  Tong-Ming Fu

    发明人： John Shiver ,  Helen Perry ,  Danilo Casimiro ,  Tong-Ming Fu

    IPC分类号： A61K48/00

    CPC分类号： C07K14/005 ,  A61K2039/53 ,  C07H21/02 ,  C12N2740/16222 ,  C12N2740/16234 ,  C12N2800/22

    摘要： Pharmaceutical compositions which comprise HIV Pol DNA vaccines are disclosed, along with the production and use of these DNA vaccines. The pol-based DNA vaccines of the invention are administered directly introduced into living vertebrate tissue, preferably humans, and preferably express inactivated versions of the HIV Pol protein devoid of protease, reverse transcriptase activity, RNase H activity and integrase activity, inducing a cellular immune response which specifically recognizes human immunodeficiency virus-1 (HIV-1). The DNA molecules which comprise the open reading frame of these DNA vaccines are synthetic DNA molecules encoding codon optimized HIV-1 Pol and codon optimized inactive derivatives of optimized HIV-1 Pol, including DNA molecules which encode inactive Pol proteins which comprise an amino terminal leader peptide.

    摘要翻译： 公开了包含HIV Pol DNA疫苗的药物组合物以及这些DNA疫苗的生产和使用。 将本发明的基于pol的DNA疫苗直接施用于活的脊椎动物组织，优选人，并且优选表达不含蛋白酶的HIV Pol蛋白，逆转录酶活性，RNase H活性和整合酶活性的失活形式，诱导细胞免疫 具体承认人体免疫缺陷病毒-1（HIV-1）的反应。 构成这些DNA疫苗的开放阅读框架的DNA分子是编码经优化的HIV-1 Pol的密码子优化的HIV-1 Pol和密码子优化的非活性衍生物的合成DNA分子，其包括编码无效Pol蛋白的DNA分子，其包含氨基末端引物 肽。