公开(公告)号：US06743431B2

公开(公告)日：2004-06-01

申请号：US10093582

申请日：2002-03-08

申请人： Gerald B. Pier

发明人： Gerald B. Pier

IPC分类号： A61K39085

CPC分类号： C12R1/46 ,  A61K38/00 ,  A61K39/00 ,  A61K39/085 ,  C07K16/1271 ,  C12Q1/06 ,  G01N2333/31 ,  Y10S435/82

摘要： A substantially pure capsular exopolysaccharide adhesin of coagulaso-negative staphylococcal strains, and a general method to prepare such adhesins, are described. Vaccines composed of such adhesins, and uses of such adhesins to produce polyclonal and mono-clonal antibodies against such adhesins, are also disclosed. The adhesins are useful in coating polymeric medical materials to prevent colonization by coagulase-negative staphylococcal strains, and as a probe in selecting desirable polymeric medical materials. Such adhesin antibodies are useful in vivo to prevent infection by noso-comial coagulase-negative staphylococcal strains, in assays for the detection of such bacteria, in assays for the estimation of such adhesins in complex mixtures, and as an affinity chromatography matrix.

摘要翻译： 描述了凝固阴性葡萄球菌菌株的基本上纯的荚膜外多糖粘附素和制备这种粘附素的一般方法。 还公开了由这种粘附素组成的疫苗以及这些粘附素的用途来产生针对这种粘附素的多克隆和单克隆抗体。 粘附素可用于涂覆聚合物医疗材料以防止凝固酶阴性葡萄球菌菌株的定居，以及作为选择期望的聚合物材料的探针。 这种粘附素抗体在体内可用于在复合混合物中用于估计这种粘附素的测定法和亲和层析基质中用于防止由嗜酸性凝血酶阴性葡萄球菌菌株感染，用于检测此类细菌的检测方法。

公开(公告)号：US06391315B1

公开(公告)日：2002-05-21

申请号：US08509630

申请日：1995-07-31

申请人： Takashi Takahashi ,  Takeji Sasaki ,  Yuzuru Iwai ,  Takashi Hashimoto

发明人： Takashi Takahashi ,  Takeji Sasaki ,  Yuzuru Iwai ,  Takashi Hashimoto

IPC分类号： A61K39085

CPC分类号： C07K16/18 ,  A61K38/00 ,  A61K39/085

摘要： An antigenic composition is derived from surface extracted protein of cell wall surfaces and the culture supernatant extract of Staphylococci. The strain is highly virulent and &bgr; hemolytic on blood agar plate. They are mixed and purified by ion exchange and gel filtration column chromatography. This preparation method can be used in all Gram-positive bacilli. The antigens, having molecular weight of about 10,000-70,000 are certain kinds of glycoprotein comprising proteins (ca. 10-20%) and carbohydrates (ca. 75-90%). They are extracted from the cells with the use of a hypertonic buffer solution of pH 6.5-8.5 at a temperature below the denaturing point of the antigenic protein, and are salted out with ammonium sulfate (ca. 65-85%). The culture supernatant is extracted in the same way by salting out with ammonium sulfate (ca. 65-85%). The antigen fraction from both cell wall and culture supernatant is obtained in such an operation. The antigen can be used as a preparation antigen to Staphylococcus antigen. Namely, the antibody obtained from mammal and avian immunized by this antigen can be used to treat the above-described infections. The composition containing the antibody provides a preventive effect.

摘要翻译： 抗原组成来源于细胞壁表面提取的蛋白质和葡萄球菌的培养上清液提取物。 该菌株在血琼脂平板上具有高毒性和β溶血性。 它们通过离子交换和凝胶过滤柱色谱法混合和纯化。 这种制备方法可用于所有革兰阳性杆菌。 具有约10,000-70,000分子量的抗原是某些种类的包含蛋白质（约10-20％）和碳水化合物（约75-90％）的糖蛋白。 在低于抗原蛋白变性点的温度下，使用pH 6.5-8.5的高渗缓冲溶液从细胞中提取它们，并用硫酸铵（约65-85％）盐析。 通过用硫酸铵盐析（约65-85％），以相同的方式提取培养物上清液。 在这种操作中获得来自细胞壁和培养上清液的抗原级分。 抗原可用作葡萄球菌抗原的制备抗原。 也就是说，从哺乳动物获得的抗体和由该抗原免疫的鸟类可以用于治疗上述感染。 含有抗体的组合物提供预防效果。

公开(公告)号：US06703025B1

公开(公告)日：2004-03-09

申请号：US09386959

申请日：1999-08-31

申请人： Joseph M. Patti ,  Timothy J. Foster ,  Magnus Hook

发明人： Joseph M. Patti ,  Timothy J. Foster ,  Magnus Hook

IPC分类号： A61K39085

CPC分类号： C07K16/1271 ,  A61K39/085

摘要： 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 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 at least a collagen binding protein or peptide (or an appropriate site directed mutated sequence thereof) such as CNA, or a protein or fragment with sufficiently high homology thereto, in combination with a fibrinogen binding protein, preferably Clumping factor A (“ClfA”) or Clumping factor B (“ClfB”), or a useful fragment thereof or a protein or fragment with sufficiently high homology thereto. The vaccines and products of the present invention are advantageous in that they respond to the urgent need of the medical community for a substitute for small molecule antibiotics, which are rapidly losing effectiveness and provide effective combinations of the large number of known bacterial surface adhesins which can impart effective protection against a broad spectrum of bacterial infections.

摘要翻译： 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，提供了一种组合物，其包含至少一种胶原结合蛋白或肽（或其适当的定点突变的序列），例如CNA或与其具有足够高同源性的蛋白质或片段，与 纤维蛋白原结合蛋白，优选结合因子A（“ClfA”）或凝集因子B（“ClfB”）或其有用片段或与其同源性具有足够高同源性的蛋白质或片段。 本发明的疫苗和产品是有利的，因为它们响应医学界迫切需要替代小分子抗生素，其正在快速丧失有效性并提供大量已知细菌表面粘附素的有效组合，其可以 有效保护免受广泛的细菌感染。

公开(公告)号：US06447786B1

公开(公告)日：2002-09-10

申请号：US08861476

申请日：1997-05-22

申请人： Richard P. Novick ,  Guangyong Ji ,  Ronald Beavis

发明人： Richard P. Novick ,  Guangyong Ji ,  Ronald Beavis

IPC分类号： A61K39085

CPC分类号： C07K14/31 ,  A61K38/00 ,  A61K39/00 ,  C07K16/1271

摘要： This invention provides peptides which inhibit agr transcription in S. aureus and thereby block the expression of virulence factors in S. aureus, pharmaceutical compositions comprising these peptides, as well as methods for treating or preventing an infection or disease caused by S. aureus using the peptides of the present invention.

摘要翻译： 本发明提供抑制金黄色葡萄球菌agr转录并因此阻断金黄色葡萄球菌中毒力因子的表达的肽，包含这些肽的药物组合物，以及用于治疗或预防由金黄色葡萄球菌引起的感染或疾病的方法 本发明的肽。

公开(公告)号：US06413524B1

公开(公告)日：2002-07-02

申请号：US09872047

申请日：2001-06-01

申请人： Michael T. Black ,  Karen M. O'Dwyer

发明人： Michael T. Black ,  Karen M. O'Dwyer

IPC分类号： A61K39085

CPC分类号： C07K14/31 ,  A61K38/00 ,  A61K39/00 ,  A61K48/00 ,  C12N9/52

摘要： spsA polypeptides and DNA (RNA) encoding such spsA and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such spsA for the treatment of infection, particularly bacterial infections. Antagonists against such spsA and their use as a therapeutic to treat infections, particularly bacterial infections are also disclosed. Also disclosed are diagnostic assays for detecting diseases related to the presence of spsA nucleic acid sequences and the polypeptides in a host. Also disclosed are diagnostic assays for detecting polynucleotides encoding spsA and for detecting the polypeptide in a host.

摘要翻译： 公开了编码这种spsA的spsA多肽和DNA（RNA）以及通过重组技术产生此类多肽的方法。 还公开了利用这种spsA来治疗感染，特别是细菌感染的方法。 还公开了抗这种spsA的拮抗剂及其用作治疗感染，特别是细菌感染的治疗剂。 还公开了用于检测与宿主中spsA核酸序列和多肽的存在相关的疾病的诊断测定法。 还公开了用于检测编码spsA的多核苷酸和用于在宿主中检测多肽的诊断测定法。

公开(公告)号：US06544529B1

公开(公告)日：2003-04-08

申请号：US09582692

申请日：2000-09-01

申请人： Ze'ev Trainin ,  Gabriel Leitner ,  Eugenia Liubashewsky

发明人： Ze'ev Trainin ,  Gabriel Leitner ,  Eugenia Liubashewsky

IPC分类号： A61K39085

CPC分类号： C12R1/445 ,  A61K39/085

摘要： The invention provides antigenic compositions for the vaccination of an animal against bovine mastitis caused by infection with Staphylococcus aureus. The invention also provides methods for stimulating an animal's immune system to respond to antigens derived from selected strains of Staphylococcus aureus by administering the antigenic compositions of the invention to the animal.

摘要翻译： 本发明提供用于疫苗接种疫苗的抗原组合物，用于由金黄色葡萄球菌感染引起的牛乳腺炎。 本发明还提供了通过向动物施用本发明的抗原组合物来刺激动物免疫系统对衍生自选定的金黄色葡萄球菌菌株的抗原作出反应的方法。

公开(公告)号：US06294177B1

公开(公告)日：2001-09-25

申请号：US09307775

申请日：1999-05-10

申请人： Ali Ibrahim Fattom

发明人： Ali Ibrahim Fattom

IPC分类号： A61K39085

CPC分类号： G01N33/56938 ,  A61K39/085 ,  A61K2039/505 ,  A61K2039/521 ,  A61K2039/6037 ,  C07K16/1271

摘要： A negatively-charged S. aureus antigen contains &bgr;-hexosamine as a major carbohydrate component. S. aureus strains that carry the antigen account for nearly all of the clinically significant strains of S. aureus that are not Type 5 or Type 8 strains. The antigen can be used in combination with S. aureus Type 5 polysaccharide antigen and S. aureus Type 8 polysaccharide antigen to provide nearly 100% coverage of S. aureus infection. The antigen and antibodies to the antigen are useful in kits and assays for diagnosing S. aureus infection. A whole cell vaccine of cells that contain the antigen is particularly useful in the treatment of mastitis.

摘要翻译： 负电荷的金黄色葡萄球菌抗原含有β-己糖胺作为主要的碳水化合物组分。 携带抗原的金黄色葡萄球菌菌株几乎占所有非5型或8型菌株的金黄色葡萄球菌的临床显着菌株。 抗原可与金黄色葡萄球菌5型多糖抗原和金黄色葡萄球菌8型多糖抗原组合使用，以提供近100％的金黄色葡萄球菌感染。 抗原和抗原抗体可用于诊断金黄色葡萄球菌感染的试剂盒和测定法。 含有抗原的细胞的全细胞疫苗特别可用于治疗乳腺炎。

公开(公告)号：US06255072B1

公开(公告)日：2001-07-03

申请号：US08941155

申请日：1997-09-30

申请人： Michael T. Black ,  Karen M. O'Dwyer

发明人： Michael T. Black ,  Karen M. O'Dwyer

IPC分类号： A61K39085

CPC分类号： C07K14/31 ,  A61K38/00 ,  A61K39/00 ,  A61K48/00 ,  C12N9/52

摘要： spsA polypeptides and DNA (RNA) encoding such spsA and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such spsA for the treatment of infection, particularly bacterial infections. Antagonists against such spsA and their use as a therapeutic to treat infections, particularly bacterial infections are also disclosed. Also disclosed are diagnostic assays for detecting diseases related to the presence of spsA nucleic acid sequences and the polypeptides in a host. Also disclosed are diagnostic assays for detecting polynucleotides encoding spsA and for detecting the polypeptide in a host.

摘要翻译： 公开了编码这种spsA的spsA多肽和DNA（RNA）以及通过重组技术产生此类多肽的方法。 还公开了利用这种spsA来治疗感染，特别是细菌感染的方法。 还公开了抗这种spsA的拮抗剂及其用作治疗感染，特别是细菌感染的治疗剂。 还公开了用于检测与宿主中spsA核酸序列和多肽的存在相关的疾病的诊断测定法。 还公开了用于检测编码spsA的多核苷酸和用于在宿主中检测多肽的诊断测定法。

公开(公告)号：US06824997B1

公开(公告)日：2004-11-30

申请号：US09397110

申请日：1999-09-16

申请人： Norman James Moore ,  Mary Kathleen Fent ,  Vladimir Andrei Koulchin ,  Elena Valentin Molokova

发明人： Norman James Moore ,  Mary Kathleen Fent ,  Vladimir Andrei Koulchin ,  Elena Valentin Molokova

IPC分类号： A61K39085

CPC分类号： G01N33/56944 ,  C07K16/1275 ,  G01N21/78 ,  G01N2021/752 ,  G01N2021/757 ,  G01N2021/7759 ,  G01N2333/3156 ,  G01N2400/10 ,  G01N2469/10

摘要： A process is disclosed for obtaining a C-polysaccharide cell wall antigen containing not more than about 10% protein from Streptococcus pneumoniae bacteria. The antigen thus obtained is conjugated to a spacer molecule, and the free end of the latter is then conjugated to a chromatographic affinity column. The column is then utilized to purify raw antibodies to S. pneumonia bacteria, thereby producing antigen-specific antibodies. A portion of such antibodies is conjugated to a labeling agent which displays a visible color change upon reaction of the antibodies with their antigenic binding partner and embedded in a first zone of an immunochromatographic assay device. Another portion of such antibodies is bound to the reaction zone of the device which has a view window. When a liquid sample, such as patient urine, cerebrospinal fluid or blood is applied to the first zone, the conjugate of antibodies and labeling agent and the sample move along a flow strip of bibulous material to the reaction zone wherein, if the sample contains S. pneumoniae or its cell wall antigen, a sandwich is formed among the labeled conjugate, the antigen and the bound antibodies and a color change is observed. The immunochromatographic assay thus performed is completed within about 15 minutes. This assay affords a basis for rapid and reliable diagnosis of various pathogenic states caused by S. pneumoniae including pneumonia, bronchitis, otitis media, sinusitis, meningitis, and secondary disease states that commonly occur when primary pneumonic infection caused by this bacterium persists undiminished over a time period of 3-5 days.

摘要翻译： 公开了一种从肺炎链球菌细菌获得含有不超过约10％蛋白质的C-多糖细胞壁抗原的方法。 由此获得的抗原与间隔分子缀合，然后将后者的自由末端与色谱亲和柱结合。 然后将柱用于纯化对肺炎链球菌细菌的原始抗体，从而产生抗原特异性抗体。 这种抗体的一部分与标记试剂缀合，所述标记试剂在抗体与其抗原结合配偶体反应并在免疫色谱测定装置的第一区域中显示可见的颜色变化。 这种抗体的另一部分结合到具有视窗的装置的反应区。 当将液体样品（例如患者尿液，脑脊液或血液）施加到第一区时，抗体和标记试剂的结合物和样品沿着吸水材料的流动条移动到反应区，其中如果样品含有S 肺炎支原体或其细胞壁抗原，在标记的缀合物，抗原和结合的抗体之间形成夹心，并观察到颜色变化。 由此进行的免疫色谱测定在约15分钟内完成。 该测定为快速可靠地诊断由肺炎链球菌引起的各种致病状态的基础，包括肺炎，支气管炎，中耳炎，鼻窦炎，脑膜炎，以及通常在由该细菌引起的原发性肺炎感染持续不减退时发生的继发性疾病状态 时间为3-5天。

公开(公告)号：US06749858B2

公开(公告)日：2004-06-15

申请号：US10190279

申请日：2002-07-05

申请人： Christian Fritz ,  Philip Youngman ,  Luz-Maria Guzman

发明人： Christian Fritz ,  Philip Youngman ,  Luz-Maria Guzman

IPC分类号： A61K39085

CPC分类号： C07K14/32 ,  C07K14/245 ,  C07K14/3156

摘要： Disclosed are two genes, termed “yphC” and “yqjK,” found in Streptococcus pneumoniae, which are essential for survival for a wide range of bacteria. These genes and the essential polypeptides that they encode, as well as homologs and orthologs thereof, can be used to identify antibacterial agents for treating a broad spectrum of bacterial infections.

摘要翻译： 公开了在肺炎链球菌中发现的两种称为“yphC”和“yqjK”的基因，其对于广泛的细菌的存活是必需的。 这些基因及其编码的必需多肽以及其同系物和直系同源物可用于鉴定用于治疗广谱细菌感染的抗菌剂。