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    • 22. 发明授权
    • Safer attenuated varicella-zoster virus vaccines with missing or diminished latency of infection
    • 更安全的减毒水痘带状疱疹病毒疫苗缺失或减少的潜伏期的感染
    • US08916175B2
    • 2014-12-23
    • US11630147
    • 2005-06-22
    • Jeffrey I. CohenEdward M. Cox, Jr.Lesley M. Pesnicak
    • Jeffrey I. CohenEdward M. Cox, Jr.Lesley M. Pesnicak
    • A61K39/25A01N63/00C12N7/00C12N7/04
    • A61K39/25A61K39/12C12N7/00C12N2710/16734C12N2710/16761C12N2710/16762
    • Viruses having weakened ability to establish and/or maintain latency and their use as live vaccines are described. The vaccines have one or more alterations in genes that provide continued virus replication but that inhibit latency. The vaccine materials and methods for their construction are exemplified with the varicella zoster virus. Deletion of a significant portion from both copies of the varicella zoster gene ORF63 was shown to inhibit establishment of a latent infection from a live vaccine form of the virus. Insertion of an additional ORF62 gene which is partially truncated with the ORF63 deletion inhibited establishment of latency and allowed normal growth of the virus. Other desirable viral antigen encoding sequence(s) and/or cytokine genes advantageously may replace deleted genetic material to enhance a desired immunological response. Aspects of the discovery pertain to live vaccines of other viruses, and can provide a variety of vaccines having greater safety.
    • 描述了具有削弱建立和/或维持延迟的能力及其作为活疫苗的用途的病毒。 疫苗在提供持续病毒复制但抑制潜伏期的基因中具有一个或多个改变。 用于其构建的疫苗材料和方法以水痘带状疱疹病毒为例。 从水痘带状疱疹基因ORF63的两个拷贝中删除重要部分被证明可以抑制病毒活疫苗形式的潜伏感染的建立。 用ORF63缺失部分截断的另外的ORF62基因的插入抑制了潜伏期的建立并允许病毒的正常生长。 其他所需的病毒抗原编码序列和/或细胞因子基因有利地可以代替缺失的遗传物质以增强所需的免疫应答。 该发现的方面涉及其他病毒的活疫苗,并且可以提供具有更高安全性的多种疫苗。
    • 30. 发明申请
    • Assays and therapies for latent viral infection
    • US20060257428A1
    • 2006-11-16
    • US11405365
    • 2006-04-17
    • John HarleyJudith JamesKenneth Kaufman
    • John HarleyJudith JamesKenneth Kaufman
    • A61K39/25A61K39/245
    • A61K39/245A61K39/12A61K2039/545A61K2039/55566A61K2039/57C07K14/005C07K16/085C12N2710/16222C12N2710/16234
    • Compositions that bind viral proteins that are specifically expressed during the latent stage of the viral life cycle are disclosed. These compositions bind the latent viral proteins while the viral proteins are expressed in their cellular host, and provide a means for targeting cells that harbor latent virus. In a preferred embodiment the compositions are antibodies which bind the extracellular region of the latent viral protein, most preferably LMP-2A, an EBV latent protein, which are conjugated to a diagnostic or cytotoxic agent or immobilized to a solid support for removal of the infected cells. These antibodies are capable of distinguishing cells expressing EBV DNA from cells which are not expressing EBV DNA. Compositions that can be used to elicit production of these antibodies, or as a vaccine, are also disclosed. Methods for generating diagnostic or cytotoxic reagents and vaccines based on the viral epitopes that identify cells harboring latent virus are also disclosed. The antibody conjugates can be used in diagnostic assays to identify cells expressing latent viral protein and people who are harboring latent viral particles. The antibody conjugates can also be used to remove the infected cells or to kill the infected the cells. Alternatively, or in addition, the viral proteins or portions thereof can be used as a vaccine to induce an immune reaction by the host to kill the infected cells. These methods can be used to detect or treat patients harboring latent viruses like EBV and who are at risk of developing a disease such as an autoimmune disease like systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).