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    • 1. 发明授权
    • Expanding the T cell repertoire to include subdominant epitopes by vaccination with antigens delivered as protein fragments or peptide cocktails
    • 通过用作为蛋白质片段或肽鸡尾酒递送的抗原进行疫苗接种来扩展T细胞谱,以包括亚显性表位
    • US08105614B2
    • 2012-01-31
    • US11823402
    • 2007-06-27
    • Claus AagaardJes DietrichPeter Andersen
    • Claus AagaardJes DietrichPeter Andersen
    • A61K39/04A61K38/02A01N25/08
    • A61K39/00A61K39/04A61K2039/55511A61K2039/5555Y02A50/412
    • A convenient way of inducing a broad recognition of dominant and subdominant responses to epitopes of any given antigen of importance for prophylaxis or treatment of a chronic disease is provided. The method involves by immunizing with pools of overlapping fragments (synthetic peptides, e.g., 10-30 mers with 2-20 aa overlap) of the desired antigen in appropriate adjuvants. The T cell repertoire is primed to include not only the immunodominant epitope recognized when the intact molecule is used for immunization and induced by the chronic infection itself, but induce a much broader and balanced response to a number of the subdominant epitopes as well. The vaccination with peptide mix induces a T-cell response that includes response to subdominant epitopes is important for protection against chronic disease that on their own induces a response focused only on immunodominant epitopes. The major advantage of the present invention is that it requires no prior knowledge of the precise localization and identity of the subdominant epitopes and their recognition in a human population, but expands the T-cell repertoire and thereby the total number of epitopes recognized by specific T cells primed by vaccination from a few immunodominant epitopes to a multiple of epitopes.
    • 提供了一种方便的方法来诱导对预防或治疗慢性疾病具有重要意义的任何给定抗原的表位的显性和亚显性反应的广泛认识。 该方法涉及通过用合适的佐剂中的所需抗原的重叠片段(合成肽,例如,10-20个重叠的2-20个重叠)的池进行免疫。 引导T细胞谱不仅包括当完整分子用于免疫并由慢性感染本身诱导时识别的免疫显性表位,而且还诱导对多个亚显性表位的更广泛和平衡的响应。 用肽混合物接种诱导T细胞应答,其包括对次优势表位的应答对于针对仅针对免疫显性表位的反应的慢性疾病的保护是重要的。 本发明的主要优点在于,它不需要在人群中亚显性表位的精确定位和识别的先验知识,而且扩展了T细胞谱,从而扩展了特定T识别的表位总数 通过从几个免疫显性表位接种到多个表位而引发的细胞。
    • 2. 发明授权
    • Vaccines comprising TB10.4
    • 疫苗包含TB10.4
    • US08557258B2
    • 2013-10-15
    • US13221211
    • 2011-08-30
    • Jes DietrichClaus AagaardPeter Andersen
    • Jes DietrichClaus AagaardPeter Andersen
    • A61K39/00A61K39/38A61K39/02A61K39/04
    • A61K39/04A61K2039/545A61K2039/55516A61K2039/55561
    • Vaccination with the combination of Ag85B-TB10.4 and IC31® adjuvant generated a high amount of polyfunctional CD4+T cells expressing high levels of IFN-γ, TNF-α, and IL-2. This in turn led to significant protection against infection with M. tuberculosis in the mouse aerosol challenge model of tuberculosis. Both the immunogenicity of the vaccine and its ability to protect against TB infection was highly dependent on the antigen dose. Thus, whereas the standard antigen dose of 5 μg, as well as 15 μg, did not induce significant protection against M. tuberculosis, reducing the dose to 0.5 μg increased both the immunogenicity of the vaccine as well as its protective efficacy to a level comparable to that observed in BCG vaccinated mice. Thus, the IC31® adjuvant, with the specified antigen dose, can induce a strong protective Th1 response against M. tuberculosis.
    • 使用Ag85B-TB10.4和IC31®佐剂的组合进行疫苗接种,产生大量表达高水平IFN-γ,TNF-α和IL-2的多功能CD4 + T细胞。 这反过来又导致了结核病小鼠气溶胶攻击模型中结核分枝杆菌感染的重大保护。 疫苗的免疫原性及其抗TB感染的能力都高度依赖于抗原剂量。 因此,尽管5杯以及15杯的标准抗原剂量没有诱导对结核分枝杆菌的显着保护,但将剂量降低至0.5杯可将疫苗的免疫原性以及其保护功效提高到可比水平 到BCG接种的小鼠中观察到的。 因此,具有特定抗原剂量的IC31®佐剂可以诱导针对结核分枝杆菌的强烈的保护性Th1应答。
    • 3. 发明申请
    • Expanding the T cell repertoire to include subdominant epitopes by vaccination with antigens delivered as protein fragments or peptide cocktails
    • 通过用作为蛋白质片段或肽鸡尾酒递送的抗原进行疫苗接种来扩展T细胞谱,以包括亚显性表位
    • US20080008724A1
    • 2008-01-10
    • US11823402
    • 2007-06-27
    • Claus AagaardJes DietrichPeter Andersen
    • Claus AagaardJes DietrichPeter Andersen
    • A61K39/00A61K39/002A61K39/04A61K39/12A61P43/00C12P21/04
    • A61K39/00A61K39/04A61K2039/55511A61K2039/5555Y02A50/412
    • A convenient way of inducing a broad recognition of dominant and subdominant responses to epitopes of any given antigen of importance for prophylaxis or treatment of a chronic disease is provided. The method involves by immunizing with pools of overlapping fragments (synthetic peptides, e.g., 10-30 mers with 2-20 aa overlap) of the desired antigen in appropriate adjuvants. The T cell repertoire is primed to include not only the immunodominant epitope recognized when the intact molecule is used for immunization and induced by the chronic infection itself, but induce a much broader and balanced response to a number of the subdominant epitopes as well. The vaccination with peptide mix induces a T-cell response that includes response to subdominant epitopes is important for protection against chronic disease that on their own induces a response focused only on immunodominant epitopes. The major advantage of the present invention is that it requires no prior knowledge of the precise localisation and identity of the subdominant epitopes and their recognition in a human population, but expands the T-cell repertoire and thereby the total number of epitopes recognized by specific T cells primed by vaccination from a few immunodominant epitopes to a multiple of epitopes.
    • 提供了一种方便的方法来诱导对预防或治疗慢性疾病具有重要意义的任何给定抗原的表位的显性和亚显性反应的广泛认识。 该方法涉及通过用合适的佐剂中的所需抗原的重叠片段(合成肽,例如,10-20个重叠的2-20个重叠)的池进行免疫。 引导T细胞谱不仅包括当完整分子用于免疫并由慢性感染本身诱导时识别的免疫显性表位,而且还诱导对多个亚显性表位的更广泛和平衡的响应。 用肽混合物接种诱导T细胞应答,其包括对次优势表位的应答对于针对仅针对免疫显性表位的反应的慢性疾病的保护是重要的。 本发明的主要优点在于,它不需要在人群中亚显性表位的精确定位和识别的先验知识,而且扩展了T细胞谱,从而扩展了特定T识别的表位总数 通过从几个免疫显性表位接种到多个表位而引发的细胞。
    • 4. 发明申请
    • VACCINES COMPRISING TB 10.4
    • 包含结核病的疫苗10.4
    • US20100015171A1
    • 2010-01-21
    • US12500881
    • 2009-07-10
    • Jes DietrichClaus AagaardPeter Andersen
    • Jes DietrichClaus AagaardPeter Andersen
    • A61K39/04A61K38/16C07K14/35A61P37/02
    • A61K39/04A61K2039/545A61K2039/55516A61K2039/55561
    • Vaccination with the combination of Ag85B-TB10.4 and IC31® adjuvant generated a high amount of polyfunctional CD4+T cells expressing high levels of IFN-γ, TNF-α, and IL-2. This in turn led to significant protection against infection with M. tuberculosis in the mouse aerosol challenge model of tuberculosis. Both the immunogenicity of the vaccine and its ability to protect against TB infection was highly dependent on the antigen dose. Thus, whereas the standard antigen dose of 5 μg, as well as 15 μg, did not induce significant protection against M. tuberculosis, reducing the dose to 0.5 μg increased both the immunogenicity of the vaccine as well as its protective efficacy to a level comparable to that observed in BCG vaccinated mice. Thus, the IC31® adjuvant, with the specified antigen dose, can induce a strong protective Th1 response against M. tuberculosis.
    • 使用Ag85B-TB10.4和IC31(R)佐剂的组合进行疫苗接种产生大量表达高水平IFN-γ,TNF-α和IL-2的多功能CD4 + T细胞。 这反过来又导致了结核病小鼠气溶胶攻击模型中结核分枝杆菌感染的重大保护。 疫苗的免疫原性及其抗TB感染的能力都高度依赖于抗原剂量。 因此,尽管5杯以及15杯的标准抗原剂量没有诱导对结核分枝杆菌的显着保护,但将剂量降低至0.5杯可将疫苗的免疫原性以及其保护功效提高到可比水平 到BCG接种的小鼠中观察到的。 因此,具有特定抗原剂量的IC31R佐剂可以诱导针对结核分枝杆菌的强烈的保护性Th1应答。