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    Modified HCV peptide vaccines
    1.
    发明授权
    Modified HCV peptide vaccines 失效
    改良的HCV肽疫苗

    公开(公告)号：US06685944B1

    公开(公告)日：2004-02-03

    申请号：US09763260

    申请日：2001-10-19

    申请人： Jay A. Berzofsky ,  C. David Pendleton ,  Stephen M. Feinstone ,  Marian E. Major ,  Pablo Sarobe

    发明人： Jay A. Berzofsky ,  C. David Pendleton ,  Stephen M. Feinstone ,  Marian E. Major ,  Pablo Sarobe

    IPC分类号： A61K3929

    CPC分类号： C07K14/005 ,  A61K39/00 ,  A61K39/12 ,  A61K39/29 ,  A61K2039/53 ,  A61K2039/55522 ,  A61K2039/55538 ,  A61K2039/55566 ,  A61K2039/57 ,  C12N2710/24143 ,  C12N2770/24222 ,  C12N2770/24234

    摘要： The present invention provides 1) an isolated peptide having the amino acid sequence DLMGYIPAV, (SEQ ID NO: 1); 2) an isolated HCV core polypeptide comprising an L→A substitution at amino acid position 139; 3) an isolated HCV core polypeptide having the amino acid sequence of SEQ ID NO: 2; and 4) a fragment of an HCV core polypeptide having fewer amino acids than the entire HCV core polypeptide and comprising the amino acid sequence SEQ ID NO: 1. Also provided are nucleic acids which encode the peptides and polypeptides of this invention, vectors comprising the nucleic acids of this invention and cells comprising the vectors and nucleic acids of this invention. The present invention further provides methods of producing an immune response in a subject and/or treating or preventing HCV infection in a subject, comprising administering to the subject, or to a cell of the subject, any of the compositions of this invention.

    摘要翻译： 本发明提供1）具有氨基酸序列DLMGYIPAV（SEQ ID NO：1）的分离肽; 2）在氨基酸位置139包含L> A取代的分离的HCV核心多肽; 3）具有SEQ ID NO：2的氨基酸序列的分离的HCV核心多肽; 和4）具有比整个HCV核心多肽更少的氨基酸并且包含氨基酸序列SEQ ID NO：1的HCV核心多肽的片段。还提供编码本发明的肽和多肽的核酸，其包含 本发明的核酸和包含本发明的载体和核酸的细胞。 本发明进一步提供了在受试者中产生免疫应答和/或治疗或预防受试者的HCV感染的方法，其包括对受试者或受试者的细胞施用任何本发明的组合物。

    Modified HCV peptide vaccines
    2.
    发明授权
    Modified HCV peptide vaccines 失效
    改良的HCV肽疫苗

    公开(公告)号：US07074410B2

    公开(公告)日：2006-07-11

    申请号：US10770117

    申请日：2004-02-02

    申请人： Jay A. Berzofsky ,  Stephen M. Feinstone ,  Marian E. Major ,  Pablo Sarobe

    发明人： Jay A. Berzofsky ,  Stephen M. Feinstone ,  Marian E. Major ,  Pablo Sarobe

    IPC分类号： A61K39/00 ,  A61K39/12 ,  A61K39/29 ,  C07H21/00 ,  C07H21/04

    CPC分类号： C07K14/005 ,  A61K39/00 ,  A61K39/12 ,  A61K39/29 ,  A61K2039/53 ,  A61K2039/55522 ,  A61K2039/55538 ,  A61K2039/55566 ,  A61K2039/57 ,  C12N2710/24143 ,  C12N2770/24222 ,  C12N2770/24234

    摘要： Provided are an isolated peptide having the amino acid sequence DLMGYIPAV (SEQ ID NO: 1), an isolated HCV core polypeptide comprising an L→A substitution at amino acid position 139, an isolated HCV core polypeptide having the amino acid sequence of SEQ ID NO: 2, and a fragment of an HCV core polypeptide having fewer amino acids than the entire HCV core polypeptide and comprising the amino acid sequence of SEQ ID NO:1. Also provided are nucleic acids which encode the peptides and polypeptides of this invention, vectors comprising the nucleic acids of this invention and cells comprising the vectors and nucleic acids of this invention. Further provided are methods of producing an immune response in a subject and/or treating or preventing HCV infection in a subject, comprising administering to the subject, or to a cell of the subject, any of the compositions of this invention.

    摘要翻译： 提供了具有氨基酸序列DLMGYIPAV（SEQ ID NO：1）的分离的肽，在氨基酸位置139包含L> A取代的分离的HCV核心多肽，具有SEQ ID NO：1的氨基酸序列的分离的HCV核心多肽 NO：2和HCV核心多肽的片段，其具有比整个HCV核心多肽更少的氨基酸并且包含SEQ ID NO：1的氨基酸序列。 还提供了编码本发明的肽和多肽的核酸，包含本发明的核酸的载体和包含本发明的载体和核酸的细胞。 还提供了在受试者中产生免疫应答和/或治疗或预防受试者的HCV感染的方法，包括向受试者或受试者的细胞施用本发明的任何组合物。

    Modified HCV peptide immunogens
    3.
    发明授权
    Modified HCV peptide immunogens 失效
    改良的HCV肽免疫原

    公开(公告)号：US07341726B2

    公开(公告)日：2008-03-11

    申请号：US11429670

    申请日：2006-05-05

    申请人： Jay A. Berzofsky ,  Pablo Sarobe ,  Stephen M. Feinstone ,  Marian E. Major

    发明人： Jay A. Berzofsky ,  Pablo Sarobe ,  Stephen M. Feinstone ,  Marian E. Major

    IPC分类号： A61K39/00 ,  A61K39/12 ,  A61K39/29 ,  C07H21/04 ,  C12N15/00

    CPC分类号： C07K14/005 ,  A61K39/00 ,  A61K39/12 ,  A61K39/29 ,  A61K2039/53 ,  A61K2039/55522 ,  A61K2039/55538 ,  A61K2039/55566 ,  A61K2039/57 ,  C12N2710/24143 ,  C12N2770/24222 ,  C12N2770/24234

    摘要： Provided are an isolated peptide having the amino acid sequence DLMGYIPAV (SEQ ID NO: 1), an isolated HCV core polypeptide comprising an L→A substitution at amino acid position 139, an isolated HCV core polypeptide having the amino acid sequence of SEQ ID NO: 2, and a fragment of an HCV core polypeptide having fewer amino acids than the entire HCV core polypeptide and comprising the amino acid sequence of SEQ ID NO:1. Also provided are nucleic acids which encode the peptides and polypeptides of this invention, vectors comprising the nucleic acids of this invention and cells comprising the vectors and nucleic acids of this invention. Further provided are methods of producing an immune response in a subject and/or treating or preventing HCV infection in a subject, comprising administering to the subject, or to a cell of the subject, any of the compositions of this invention.

    摘要翻译： 提供了具有氨基酸序列DLMGYIPAV（SEQ ID NO：1）的分离的肽，在氨基酸位置139包含L> A取代的分离的HCV核心多肽，具有SEQ ID NO：1的氨基酸序列的分离的HCV核心多肽 NO：2和HCV核心多肽的片段，其具有比整个HCV核心多肽更少的氨基酸并且包含SEQ ID NO：1的氨基酸序列。 还提供了编码本发明的肽和多肽的核酸，包含本发明的核酸的载体和包含本发明的载体和核酸的细胞。 还提供了在受试者中产生免疫应答和/或治疗或预防受试者的HCV感染的方法，包括向受试者或受试者的细胞施用本发明的任何组合物。

    Identification of peptides that stimulate hepatitis C virus specific cytotoxic T cells
    4.
    发明授权
    Identification of peptides that stimulate hepatitis C virus specific cytotoxic T cells 失效
    鉴定刺激丙型肝炎病毒特异性细胞毒性T细胞的肽

    公开(公告)号：US5980899A

    公开(公告)日：1999-11-09

    申请号：US894063

    申请日：1992-06-10

    申请人： Jay A. Berzofsky ,  Mutsunori Shirai ,  Toshitaka Akatsuka ,  Stephen M. Feinstone

    发明人： Jay A. Berzofsky ,  Mutsunori Shirai ,  Toshitaka Akatsuka ,  Stephen M. Feinstone

    IPC分类号： G01N33/53 ,  A61K38/00 ,  A61K39/00 ,  A61K39/29 ,  A61P31/12 ,  A61P37/00 ,  C07K7/06 ,  C07K7/08 ,  C07K14/18 ,  G01N33/569 ,  G01N33/576 ,  A61K39/12 ,  C07K2/00

    CPC分类号： C07K14/005 ,  A61K39/00 ,  C12N2770/24222

    摘要： The cytotoxic T cell response to the protein encoded by the NS5 region of hepatitis C virus was determined using 28 peptides from NS5 which were selected by an amphipathicity algorithm as candidates for T cell epitopes. In BALB/c mice, a single relatively conserved epitope represented by a 16-residue synthetic peptide was presented by D.sup.d class I major histocompatibility complex (MHC) molecules to conventional CD4.sup.- CD8.sup.+ CTL. An exemplary peptide, which represents amino acid residues 2422-2437 of the polyprotein of the Chiron HCV1 isolate, had the amino acid sequence MSYSWTGALVTPCAAE [SEQ ID NO: 1]. A CTL line specific for this peptide recognized the two known natural variants of this NS5 sequence, each with conservative substitutions. Thus, CTL can recognize the product of the HCV NS5 gene, the probable RNA polymerase, in association with class I MHC molecules on model target cells and may recognize the same epitope on hepatocytes or any other cells infected with the virus.

    摘要翻译： 使用来自NS5的28个肽来确定由丙型肝炎病毒的NS5区编码的蛋白质的细胞毒性T细胞应答，其通过两亲性算法选择作为T细胞表位的候选物。 在BALB / c小鼠中，通过Dd I类主要组织相容性复合物（MHC）分子向常规CD4-CD8 + CTL提供了由16个残基合成肽表示的单个相对保守的表位。 表示Chiron HCV1分离物的多蛋白的氨基酸残基2422-2437的示例性肽具有氨基酸序列MSYSWTGALVTPCAAE [SEQ ID NO：1]。 该肽特异的CTL系识别了NS5序列的两个已知天然变体，每个具有保守取代。 因此，CTL可以识别HCV NS5基因（可能的RNA聚合酶）与模型靶细胞上的I类MHC分子相关联的产物，并且可以识别肝细胞或感染病毒的任何其它细胞上的相同表位。

    Peptides which elicit a high neutralizing antibody titer, cytotoxic T lymphocyte response and T helper cell response in a broad range of MHC type recipients
    5.
    发明授权
    Peptides which elicit a high neutralizing antibody titer, cytotoxic T lymphocyte response and T helper cell response in a broad range of MHC type recipients 失效
    在广泛的MHC型受体中引发高中和抗体滴度，细胞毒性T淋巴细胞反应和T辅助细胞应答的肽

    公开(公告)号：US07094405B1

    公开(公告)日：2006-08-22

    申请号：US09455076

    申请日：1999-12-06

    申请人： Jay A. Berzofsky ,  Jeffrey D. Ahlers ,  C. David Pendleton ,  Peter Nara ,  Mutsunori Shirai

    发明人： Jay A. Berzofsky ,  Jeffrey D. Ahlers ,  C. David Pendleton ,  Peter Nara ,  Mutsunori Shirai

    IPC分类号： A61K39/21

    CPC分类号： C07K14/005 ,  A61K38/03 ,  A61K38/55 ,  A61K38/556 ,  A61K39/00 ,  A61K39/12 ,  A61K39/21 ,  A61K2039/545 ,  A61K2039/55516 ,  A61K2039/55566 ,  A61K2039/55577 ,  A61K2039/57 ,  A61K2039/645 ,  C07K2319/00 ,  C12N2740/16122 ,  C12N2740/16134 ,  Y02A50/412 ,  A61K2300/00

    摘要： Peptide constructs comprised of multideterminant T helper peptides from the envelope glycoprotein of HIV previously identified to induce proliferative responses in four different haplotypes of mice and IL-2 responses in 52-73% of HIV positive, flu positive patients (cluster peptides), were co-linearly synthesized with the peptide 18 of the V3 loop of HIV-1 gp 160, corresponding to the principal neutralizing determinant of HIV-IIIB and also shown to contain a dominant CTL epitope. Cognate help for peptide 18 antibody was elicited following a single immunization in all strains of mice which had previously responded to a T cell epitope encompassed by the peptides. In two strains of mice, the level of neutralizing antibody achieved was comparable to levels adequate for protection from homologous viral challenge in chimpanzees. After a single boost, much higher antibody titers for 90% neutralization in the range of 1:1000 to 1:16,000 were achieved. Spleen cells from mice of three distinct MHC haplotypes sharing the Dd class I MHC molecule but with different class II molecules, immunized with the compound peptides, exhibited enhanced gp160-specific CTL activity.

    摘要翻译： 由先前鉴定为在四种不同单倍型小鼠中诱导增殖反应的HIV的多重决定子T辅助肽和52-73％的HIV阳性患者（簇肽）中的IL-2应答组成的多肽构建体由co 与HIV-1 gp 160的V3环的肽18线性合成，对应于HIV-IIIB的主要中和决定簇，并且还显示含有显性CTL表位。 在先前对肽包含的T细胞表位作出反应的所有小鼠菌株中进行单次免疫后，引发了针对肽18抗体的协同帮助。 在两种小鼠中，达到的中和抗体水平与足以保护黑猩猩同源病毒攻击的水平相当。 在单次加强后，实现了在1:1000至1：16,000范围内高达90％中和的高得多的抗体滴度。 来自共享第一类MHC分子但具有用化合物肽免疫的不同II类分子的三种不同MHC单元型的小鼠的脾细胞表现出增强的gp160特异性CTL活性。

    Multideterminant peptides that elicit helper T-lymphocyte cytotoxic T-lymphocyte and neutralizing antibody responses against HIV-1
    6.
    发明授权
    Multideterminant peptides that elicit helper T-lymphocyte cytotoxic T-lymphocyte and neutralizing antibody responses against HIV-1 失效
    引起辅助T淋巴细胞细胞毒性T淋巴细胞和中和抗HIV-1抗体的多决定肽

    公开(公告)号：US06294322B1

    公开(公告)日：2001-09-25

    申请号：US08060988

    申请日：1993-05-14

    申请人： Jay A. Berzofsky ,  Jeffrey D. Ahlers ,  C. David Pendleton ,  Peter Nara ,  Mutsunori Shirai

    发明人： Jay A. Berzofsky ,  Jeffrey D. Ahlers ,  C. David Pendleton ,  Peter Nara ,  Mutsunori Shirai

    IPC分类号： C12Q170

    CPC分类号： C07K14/005 ,  A61K38/03 ,  A61K38/55 ,  A61K38/556 ,  A61K39/00 ,  A61K39/12 ,  A61K39/21 ,  A61K2039/545 ,  A61K2039/55516 ,  A61K2039/55566 ,  A61K2039/55577 ,  A61K2039/57 ,  A61K2039/645 ,  C07K2319/00 ,  C12N2740/16122 ,  C12N2740/16134 ,  Y02A50/412 ,  A61K2300/00

    摘要： Peptide constructs comprised of multideterminant T helper peptides from the envelope glycoprotein of HIV previously identified to induce proliferative responses in four different haplotypes of mice and IL-2 responses in 52-73% of HIV positive, flu positive patients (cluster peptides), were co-linearly synthesized with the peptide 18 of the V3 loop of HIV-1 gp 160, corresponding to the principal neutralizing determinant of HIV-IIIB and also shown to contain a dominant CTL epitope. Cognate help for peptide 18 antibody was elicited following a single immunization in all strains of mice which had previously responded to a T cell epitope encompassed by the peptides. In two strains of mice, the level of neutralizing antibody achieved was comparable to levels adequate for protection from homologous viral challenge in chimpanzees. After a single boost, much higher antibody titers for 90% neutralization in the range of 1:1000 to 1:16,000 were achieved. Spleen cells from mice of three distinct MHC haplotypes sharing the Dd class I MHC molecule but with different class II molecules, immunized with the compound peptides, exhibited enhanced gp160-specific CTL activity.

    摘要翻译： 由先前鉴定为在四种不同单倍型小鼠中诱导增殖反应的HIV的多重决定子T辅助肽和52-73％的HIV阳性患者（簇肽）中的IL-2应答组成的多肽构建体由co 与HIV-1 gp 160的V3环的肽18线性合成，对应于HIV-IIIB的主要中和决定簇，并且还显示含有显性CTL表位。 在先前对肽包含的T细胞表位作出反应的所有小鼠菌株中进行单次免疫后，引发了针对肽18抗体的协同帮助。 在两种小鼠中，达到的中和抗体水平与足以保护黑猩猩同源病毒攻击的水平相当。 在单次加强后，实现了在1:1000至1：16,000范围内高达90％中和的高得多的抗体滴度。 来自共享Dd I类MHC分子但具有用化合物肽免疫的不同II类分子的三种不同MHC单元型的小鼠的脾细胞表现出增强的gp160特异性CTL活性。

    Immunogenic peptides for the treatment of prostate and breast cancer
    10.
    发明授权
    Immunogenic peptides for the treatment of prostate and breast cancer 有权
    用于治疗前列腺癌和乳腺癌的免疫原性肽

    公开(公告)号：US08043623B2

    公开(公告)日：2011-10-25

    申请号：US12430837

    申请日：2009-04-27

    申请人： Jay A. Berzofsky ,  SangKon Oh ,  Ira Pastan

    发明人： Jay A. Berzofsky ,  SangKon Oh ,  Ira Pastan

    IPC分类号： C07K5/00

    CPC分类号： C07K14/4748 ,  A61K39/00 ,  A61K48/00 ,  A61K2039/5154 ,  A61K2039/5158 ,  A61K2039/53 ,  A61K2039/57

    摘要： Immunogenic T-cell receptor gamma Alternate Reading Frame Protein (TARP) polypeptides are disclosed herein. These immunogenic TARP polypeptides include nine consecutive amino acids of the amino acid sequence set forth as SEQ ID NO: 9 and do not comprise amino acids 1-26 or amino acids 38-58 of SEQ ID NO: 1. Several specific, non-limiting examples of these polypeptides are set forth as SEQ ID NOs: 3-7. Nucleic acids encoding these polypeptides, and host cells transfected with these nucleic acids, are also disclosed. Methods of using these polypeptides, and polynucleotides encoding these polypeptides, for the treatment of breast and prostate cancer are also disclosed.

    摘要翻译： 本文公开了免疫原性T细胞受体γ替代阅读框蛋白（TARP）多肽。 这些免疫原性TARP多肽包括SEQ ID NO：9所示的氨基酸序列的9个连续氨基酸，并且不包含SEQ ID NO：1的氨基酸1-26或氨基酸38-58。几个具体的，非限制性的 这些多肽的实例如SEQ ID NO：3-7所示。 还公开了编码这些多肽的核酸和用这些核酸转染的宿主细胞。 还公开了使用这些多肽的方法和编码这些多肽的多核苷酸用于治疗乳腺癌和前列腺癌。