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    • 2. 发明授权
    • Extracellular matrix-binding proteins from Staphylococcus aureus
    • 来自金黄色葡萄球菌的细胞外基质结合蛋白
    • US07381793B2
    • 2008-06-03
    • US10744672
    • 2003-12-24
    • Joseph M. PattiTimothy J. FosterElisabet JosefssonDeidre Ni EidhinMagnus A. O. HookSamuel E. Perkins
    • Joseph M. PattiTimothy J. FosterElisabet JosefssonDeidre Ni EidhinMagnus A. O. HookSamuel E. Perkins
    • C07K1/00
    • G01N33/56938A61K38/00A61K39/00C07K14/31G01N2469/00Y10S435/975Y10S530/81Y10S530/825
    • Isolated extracellular matrix-binding proteins, designated ClfB, SdrC, SdrD and SdrE, and their corresponding amino acid and nucleic acid sequences and motifs are described. The proteins, peptides, fragments thereof or antigenic portions thereof are useful for the prevention, inhibition, treatment and diagnosis of S. aureus infection and as scientific research tools. Further, antibodies or antibody fragments to the proteins, peptides, fragments thereof or antigenic portions thereof are also useful for the prevention, inhibition, treatment and diagnosis of S. aureus infection. In particular, the proteins or antibodies thereof may be administered to wounds or used to coat biomaterials to act as blocking agents to prevent or inhibit the binding of S. aureus to wounds or biomaterials.ClfB is a cell-wall associated protein having a predicted molecular weight of approximately 88 kDa and an apparent molecular weight of approximately 124 kDa, which binds both soluble and immobilized fibrinogen. ClfB binds both the alpha and beta chains of fibrinogen and acts as a clumping factor. SdrC, SdrD and SdrE are cell-wall associated proteins that exhibit cation-dependent ligand binding to the extracellular matrix. It has been discovered that in the A region of SdrC, SdrD, SdrE, ClfA and ClfB, there is a highly conserved amino acid sequence that can be used to derive a consensus motif of TYTFTDYVD.
    • 描述了分离的细胞外基质结合蛋白,命名为ClfB,SdrC,SdrD和SdrE,以及它们相应的氨基酸和核酸序列和基序。 蛋白质,肽,其片段或其抗原部分可用于预防,抑制,治疗和诊断金黄色葡萄球菌感染以及科学研究工具。 此外,蛋白质,肽,其片段或其抗原部分的抗体或抗体片段也可用于预防,抑制,治疗和诊断金黄色葡萄球菌感染。 特别地,其蛋白质或其抗体可以施用于伤口或用于涂覆生物材料以用作阻断剂以预防或抑制金黄色葡萄球菌与伤口或生物材料的结合。 ClfB是具有约88kDa的预测分子量和约124kDa的表观分子量的细胞壁相关蛋白,其结合可溶性和固定的纤维蛋白原。 ClfB结合纤维蛋白原的α链和β链,并作为聚集因子。 SdrC,SdrD和SdrE是表现出阳离子依赖性配体结合细胞外基质的细胞壁相关蛋白。 已经发现,在SdrC,SdrD,SdrE,ClfA和ClfB的A区域中,存在可用于得到TYTFTDYVD的共有基序的高度保守的氨基酸序列。
    • 3. 发明授权
    • Staphylococcal immunotherapeutics via donor selection and donor stimulation
    • 葡萄球菌免疫治疗通过供体选择和供体刺激
    • US06692739B1
    • 2004-02-17
    • US09386960
    • 1999-08-31
    • Joseph M. PattiTimothy J. FosterMagnus Hook
    • Joseph M. PattiTimothy J. FosterMagnus Hook
    • A61K39395
    • A61K9/0019A61K39/00A61K2039/505C07K16/1271C07K2317/20C07K2317/76
    • A method and composition for the passive immunization of patients infected with or susceptible to infection from Staphylococcus bacteria such as S. aureus and S. epidermidis infection is provided that includes the selection or preparation of a donor plasma pool with high antibody titers to carefully selected Staphylococcus adhesins or MSCRAMMs, or fragments or components thereof, or sequences with substantial homology thereto. The donor plasma pool can be prepared by combining individual blood or blood component samples which have higher than normal titers of antibodies to one or more of the selected adhesins or other proteins that bind to extracellular matrix proteins, or by administering carefully selected proteins or peptides to a host to induce the expression of desired antibodies, and subsequently recovering the enhanced high titer serum or plasma pool from the treated host. In either case, the donor plasma pool is preferably purified and concentrated prior to intravenous introduction into the patient, and the present invention is advantageous in that a patient can be immunized against a wide variety of potentially dangerous staphylococcal infections. Kits for identifying potential donor with high titers of the selected adhesins are also provided. The present invention thus provides methods and compositions which can be highly effective against infections associated with Staphylococcus bacteria.
    • 提供了感染或易感染葡萄球菌如金黄色葡萄球菌和表皮葡萄球菌感染的患者的被动免疫的方法和组合物,其包括选择或制备具有高抗体滴度的供体血浆池以精心选择的葡萄球菌 粘附素或MSCRAMM,或其片段或组分,或与其基本上同源的序列。 供体血浆池可以通过将具有高于正常滴度的抗体的单个血液或血液成分样品与一种或多种所选择的粘附素或与细胞外基质蛋白结合的其它蛋白质组合,或通过将仔细选择的蛋白质或肽给予 诱导所需抗体表达的宿主,随后从被处理的宿主中回收增强的高效价血清或血浆池。 在任一情况下,供体血浆池优选在静脉内引入患者体内之前进行纯化和浓缩,本发明的优点在于可以免疫多种潜在危险的葡萄球菌感染。 还提供了用于鉴定具有高滴度选择的粘附素的潜在供体的试剂盒。 因此,本发明提供了可以高效地抵抗与葡萄球菌细菌相关的感染的方法和组合物。
    • 4. 发明授权
    • Extracellular matrix-binding proteins from staphylococcus aureus
    • 来自金黄色葡萄球菌的细胞外基质结合蛋白
    • US06680195B1
    • 2004-01-20
    • US09200650
    • 1998-11-25
    • Joseph M. PattiTimothy J. FosterElisabet JosefssonDeidre Ni EidhinMagnus A. O. HookSamuel E. Perkins
    • Joseph M. PattiTimothy J. FosterElisabet JosefssonDeidre Ni EidhinMagnus A. O. HookSamuel E. Perkins
    • C07H2104
    • G01N33/56938A61K38/00A61K39/00C07K14/31G01N2469/00Y10S435/975Y10S530/81Y10S530/825
    • Isolated extracellular matrix-binding proteins, designated ClfB, SdrC, SdrD and SdrE, and their corresponding amino acid and nucleic acid sequences and motifs are described. The proteins, peptides, fragments thereof or antigenic portions thereof are useful for the prevention, inhibition, treatment and diagnosis of S. aureus infection and as scientific research tools. Further, antibodies or antibody fragments to the proteins, peptides, fragments thereof or antigenic portions thereof are also useful for the prevention, inhibition, treatment and diagnosis of S. aureus infection. In particular, the proteins or antibodies thereof may be administered to wounds or used to coat biomaterials to act as blocking agents to prevent or inhibit the binding of S. aureus to wounds or biomaterials. ClfB is a cell-wall associated protein having a predicted molecular weight of approximately 88 kDa and an apparent molecular weight of approximately 124 kDa, which binds both soluble and immobilized fibrinogen. ClfB binds both the alpha and beta chains of fibrinogen and acts as a clumping factor. SdrC, SdrD and SdrE are cell-wall associated proteins that exhibit cation-dependent ligand binding to the extracellular matrix. It has been discovered that in the A region of SdrC, SdrD, SdrE, ClfA and ClfB, there is a highly conserved amino acid sequence that can be used to derive a consensus motif of TYTFTDYVD (SEQ ID NO: 16).
    • 描述了分离的细胞外基质结合蛋白,命名为ClfB,SdrC,SdrD和SdrE,以及它们相应的氨基酸和核酸序列和基序。 蛋白质,肽,其片段或其抗原部分可用于预防,抑制,治疗和诊断金黄色葡萄球菌感染以及科学研究工具。 此外,蛋白质,肽,其片段或其抗原部分的抗体或抗体片段也可用于预防,抑制,治疗和诊断金黄色葡萄球菌感染。 特别地,其蛋白质或其抗体可以施用于伤口或用于涂覆生物材料以用作阻断剂以预防或抑制金黄色葡萄球菌与伤口或生物材料的结合。 ClfB是具有约88kDa的预测分子量和约124kDa的表观分子量的细胞壁相关蛋白,其结合可溶性和固定的纤维蛋白原。 ClfB结合纤维蛋白原的α链和β链,并作为聚集因子。 SdrC,SdrD和SdrE是表现出阳离子依赖性配体结合细胞外基质的细胞壁相关蛋白。 已经发现,在SdrC,SdrD,SdrE,ClfA和ClfB的A区域中,存在可用于衍生TYTFTDYVD(SEQ ID NO:16)的共有基序的高度保守的氨基酸序列。
    • 9. 发明授权
    • Polypeptides and polynucleotides from coagulase-negative staphylococci
    • 来自凝固酶阴性葡萄球菌的多肽和多核苷酸
    • US06635473B1
    • 2003-10-21
    • US09386962
    • 1999-08-31
    • Timothy J. FosterKirk McCreaMagnus A. O. HookStacy DavisDeirdre Ni EidhinOrla Hartford
    • Timothy J. FosterKirk McCreaMagnus A. O. HookStacy DavisDeirdre Ni EidhinOrla Hartford
    • C07H2104
    • C07K16/1271A61K39/00A61K2039/505C07K14/31G01N33/56938
    • Isolated proteins, designated SdrF, SdrG and SdrH, and their corresponding amino acid and nucleic acid sequences are provided which are useful in the prevention and treatment of infection caused by coagulase-negative staphylococcal bacteria such as S. epidermidis. The SdrF, SdrG and SdrH proteins are cell-wall associated proteins that specifically bind host proteins and which each have a highly conserved motif of which the consensus sequence is TYTFTDYVD (SEQ ID NO:16). The proteins, antigenic portions thereof and anti-SdrF, SdrG and SdrH antibodies are also useful for the identification and diagnosis of coagulase-negative staphylococcal infections. In particular, the proteins are advantageous because they may be used as vaccine components or antibodies thereof, and they may be administered to wounds or used to coat biomaterials to act as blocking agents to prevent or inhibit the binding of coagulase-negative staphylococci to wounds or biomaterials.
    • 提供了称为SdrF,SdrG和SdrH的分离的蛋白质及其相应的氨基酸和核酸序列,其可用于预防和治疗由凝血酶阴性葡萄球菌如表皮葡萄球菌引起的感染。 SdrF,SdrG和SdrH蛋白是特异性结合宿主蛋白的细胞壁相关蛋白,其各自具有高度保守的基序,其共有序列是TYTFTDYVD(SEQ ID NO:16)。 蛋白质,其抗原部分和抗SdrF,SdrG和SdrH抗体也可用于鉴定和诊断凝固酶阴性葡萄球菌感染。 特别地,蛋白质是有利的,因为它们可以用作疫苗组分或其抗体,并且它们可以施用于伤口或用于涂覆生物材料以用作阻断剂以预防或抑制凝固酶阴性葡萄球菌与伤口的结合或 生物材料。
    • 10. 发明授权
    • Multicomponent vaccines
    • 多组分疫苗
    • US08017133B2
    • 2011-09-13
    • US12710790
    • 2010-02-23
    • Joseph M. PattiTimothy J. FosterMagnus Hook
    • Joseph M. PattiTimothy J. FosterMagnus Hook
    • A61K39/085
    • C07K16/1271A61K39/085
    • Multicomponent vaccines are provided which aid in the prevention and treatment of staphylococcal infections and which include certain selected combinations of bacterial binding proteins or fragments thereof, or antibodies to those proteins or fragments. By careful selection of the proteins, fragments, or antibodies, a vaccine is provided that imparts protection against a broad spectrum of Staphylococcus and other bacterial strains and against proteins that are expressed at different stages of the logarithmic growth curve. In one embodiment of the invention, a composition is provided that includes a fibrinogen binding domain of a fibrinogen binding protein and a bacterial component such as a capsular polysaccharide, and both active and passive vaccines based on these components are also provided, along with methods of treating infection using these compositions and vaccines.
    • 提供了有助于预防和治疗葡萄球菌感染的多组分疫苗,其包括某些所选择的细菌结合蛋白或其片段的组合,或对那些蛋白质或片段的抗体。 通过仔细选择蛋白质,片段或抗体,提供疫苗,其对广泛的葡萄球菌和其他细菌菌株和针对在对数生长曲线的不同阶段表达的蛋白质提供保护。 在本发明的一个实施方案中,提供了包括纤维蛋白原结合蛋白的纤维蛋白原结合结构域和诸如荚膜多糖的细菌组分的组合物,以及基于这些组分的主动和被动疫苗以及方法 使用这些组合物和疫苗治疗感染。