公开(公告)号：US20070054395A1

公开(公告)日：2007-03-08

申请号：US11599584

申请日：2006-11-13

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

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

IPC: C12Q1/68 ,  C12N15/00

CPC classification number: 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

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US20070077257A1

公开(公告)日：2007-04-05

申请号：US11604553

申请日：2006-11-27

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

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

IPC: A61K39/00 ,  A61K39/12

CPC classification number: A61K39/21 ,  A61K39/12 ,  A61K2039/5256 ,  A61K2039/53 ,  A61K2039/545 ,  A61K2039/55555 ,  C07K14/005 ,  C12N7/00 ,  C12N2710/10343 ,  C12N2710/10351 ,  C12N2740/16222 ,  C12N2740/16234 ,  C12N2740/16322 ,  C12N2740/16334

Abstract: First generation adenoviral vectors and-recombinant adenovirus-based HIV vaccines which contain HIV-1 gag, HIV-1 pol and/or HIV-1 nef polynucleotide pharmaceutical products, and biologically relevant modifications thereof are described. The adenovirus vaccines, when directly introduced into living vertebrate tissue, express the relevant proteins, 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, HIV-1 Pol, HIV-1 Nef, and derivatives thereof. The adenoviral vaccines of the present invention, alone or in combination, 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.

Abstract translation: 描述了含有HIV-1 gag，HIV-1 pol和/或HIV-1 nef多核苷酸药物产品的第一代腺病毒载体和基于重组腺病毒的HIV疫苗及其生物学相关的修饰。 当直接引入活的脊椎动物组织中时，腺病毒疫苗表达相关蛋白质，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，HIV-1 Pol，HIV-1 Nef的合成DNA分子及其衍生物。 本发明的单独或组合的腺病毒疫苗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。

公开(公告)号：US20050106123A1

公开(公告)日：2005-05-19

申请号：US10507098

申请日：2003-03-12

Applicant: Emilio Emini ,  John Shiver ,  Michael Chastain ,  Danilo Casimiro ,  Tong-Ming Fu ,  Xiaoping Liang

Inventor： Emilio Emini ,  John Shiver ,  Michael Chastain ,  Danilo Casimiro ,  Tong-Ming Fu ,  Xiaoping Liang

IPC: A61K39/00 ,  A61K39/21 ,  C07K14/16 ,  C12N15/861 ,  C12N15/863 ,  A61K48/00 ,  A61K39/12 ,  C12N15/867

CPC classification number: C12N15/86 ,  A61K39/12 ,  A61K39/21 ,  A61K2039/5256 ,  A61K2039/545 ,  C07K14/005 ,  C12N2710/10343 ,  C12N2710/24043 ,  C12N2710/24143 ,  C12N2740/15034 ,  C12N2740/16122 ,  C12N2740/16134 ,  C12N2740/16234 ,  C12N2830/42

Abstract: 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 wherein recombinant adenoviral and poxvirus vectors comprising exogenous genetic material encoding a common HIV antigen are administered in that order. 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.

Abstract translation: 公开了一种利用特定初始 - 加强方式诱导针对人类免疫缺陷病毒（“HIV”）的免疫应答的有效手段。 特异性初始 - 加强方案采用异源初始 - 加强方案，其中包含编码常见HIV抗原的外源遗传物质的重组腺病毒和痘病毒载体以该顺序施用。 根据所公开的方案，优选哺乳动物宿主例如商业或家庭兽医重要的人或非人哺乳动物施用于活的脊椎动物组织的疫苗表达HIV-1抗原（例如，Gag），诱导细胞免疫 专门承认艾滋病毒1的反应。 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。

公开(公告)号：US20060216272A1

公开(公告)日：2006-09-28

申请号：US10571651

申请日：2004-09-14

Applicant: Emilio Emini ,  John Shiver ,  Danilo Casimiro ,  Daria Hazuda ,  William Scheilf

Inventor： Emilio Emini ,  John Shiver ,  Danilo Casimiro ,  Daria Hazuda ,  William Scheilf

IPC: A61K48/00

CPC classification number: A61K39/21 ,  A61K39/12 ,  A61K2039/53 ,  A61K2039/545 ,  A61K2039/55 ,  C07K14/005 ,  C12N7/00 ,  C12N15/86 ,  C12N2710/10343 ,  C12N2740/15022 ,  C12N2740/15034 ,  C12N2740/15071 ,  C12N2740/16134 ,  C12N2740/16222

Abstract: The present invention provides an improved method for eliciting a therapeutic immune response in an individual infected with human immunodeficiency virus (“HIV”). The method comprises administering an adenoviral vaccine composition expressing an HIV antigen to an individual with controlled viremia. Immunization of infected individuals in this manner elicits a cellular-mediated immune response against the virus that is significant both in the level of the response and the breadth of the response. The therapeutic immune response that ensues is capable of effectively maintaining low titers of virus and, thus, offers the prospect of reducing individual dependency on antiviral therapy.

Abstract translation: 本发明提供了在感染人类免疫缺陷病毒（“HIV”）的个体中引发治疗性免疫应答的改进方法。 该方法包括向具有受控制的病毒血症的个体施用表达HIV抗原的腺病毒疫苗组合物。 以这种方式免疫感染的个体引起针对病毒的细胞介导的免疫应答，其在反应水平和反应的广度方面是显着的。 随后的治疗性免疫应答能够有效地维持低滴度的病毒，从而提供减少个体对抗病毒治疗依赖性的前景。

公开(公告)号：US20060165664A1

公开(公告)日：2006-07-27

申请号：US10507237

申请日：2003-03-12

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

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

IPC: A61K48/00 ,  A61K39/21

CPC classification number: 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

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US20050070017A1

公开(公告)日：2005-03-31

申请号：US10636730

申请日：2003-08-07

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

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

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

CPC classification number: 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

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US20080063656A1

公开(公告)日：2008-03-13

申请号：US11659671

申请日：2005-08-05

Applicant: Emilio Emini ,  John Shiver ,  Danilo Casimiro ,  Andrew Bett

Inventor： Emilio Emini ,  John Shiver ,  Danilo Casimiro ,  Andrew Bett

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

CPC classification number: 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

Abstract: 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.

Abstract translation: 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。