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1. 发明授权

US07241592B2 Cross-reactive displacing antibodies from collagen-binding proteins and method of identification and use 有权
标题翻译：来自胶原蛋白结合蛋白的交叉反应置换抗体及鉴定和使用方法
公开(公告)号：US07241592B2
公开(公告)日：2007-07-10
申请号：US09810428
申请日：2001-03-19
申请人： Magnus Hook , Yi Xu , Pietro Speziale , Livia Visal , Fabrizia Casolini , Joseph M. Patti , Pratiksha Patel , Paul Domanski
发明人： Magnus Hook , Yi Xu , Pietro Speziale , Livia Visal , Fabrizia Casolini , Joseph M. Patti , Pratiksha Patel , Paul Domanski
IPC分类号： C12P21/08 , C12N1/00 , A61K39/395 , A61K39/40 , C07K16/12
CPC分类号： C07K16/1271 , A61K39/085 , A61K2039/505 , C07K2317/76 , C07K2317/92 , C07K2319/00 , G01N33/56938 , G01N2333/31 , G01N2333/78 , G01N2500/00
摘要： Antibodies to the CNA protein and to other regions from the collagen binding domain, including domain CNA19, are provided, and antibodies produced in this manner have been shown to be cross reactive to both Staphylococcus aureus and Staphylococcus epidermidis bacteria and which can thus be used in the prevention and treatment of infections caused by both of these types of bacteria. In addition, medical instruments can be treated using the antibodies of the invention in order to reduce or eliminate the possibility of their becoming infected or further spreading the infection. In particular, the proteins are advantageous because they are cross-reactive and may thus be administered to patients so as to reduce or prevent severe infection by staphylococcal bacteria of more than one species. Antibodies generated in this manner have also been shown to exhibit displacement activity and can thus be utilized advantageously in methods wherein these antibodies will be administered to patients having pre-existing staphylococcal infections because of the ability to displace bacterial proteins from binding sites on the extracellular matrix. Finally, a method of identifying, isolating and utilizing displacing antibodies is also provided.
摘要翻译：提供了对CNA蛋白和来自胶原结合结构域的其他区域（包括结构域CNA19）的抗体，并且以这种方式产生的抗体已显示与金黄色葡萄球菌和表皮葡萄球菌交叉反应，因此可以用于预防和治疗由这两种细菌引起的感染。此外，可以使用本发明的抗体治疗医疗器械，以便减少或消除它们被感染或进一步扩散感染的可能性。特别地，蛋白质是有利的，因为它们是交叉反应性的，并且因此可以施用于患者，以便减少或预防多于一种物种的葡萄球菌细菌的严重感染。以这种方式产生的抗体也已显示出显示置换活性，因此可有利地用于其中将这些抗体施用于具有预先存在的葡萄球菌感染的患者的方法，因为能够从细胞外基质上的结合位点置换细菌蛋白质。最后，还提供了鉴定，分离和利用置换抗体的方法。

2. 发明申请

US20070122416A1 CROSS-REACTIVE DISPLACING ANTIBODIES FROM COLLAGEN-BINDING PROTEINS AND METHOD OF IDENTIFICATION AND USE 有权
标题翻译：来自胶原蛋白结合蛋白的交叉反应位移抗体及其鉴定和使用方法
公开(公告)号：US20070122416A1
公开(公告)日：2007-05-31
申请号：US09810428
申请日：2001-03-19
申请人： Magnus Hook , Yi Xu , Pietro Speziale , Livia Visal , Fabrizia Casolini , Joseph Patti , Pratiksha Patel , Paul Domanski
发明人： Magnus Hook , Yi Xu , Pietro Speziale , Livia Visal , Fabrizia Casolini , Joseph Patti , Pratiksha Patel , Paul Domanski
IPC分类号： A61K39/40 , G01N33/554 , C07K16/12
CPC分类号： C07K16/1271 , A61K39/085 , A61K2039/505 , C07K2317/76 , C07K2317/92 , C07K2319/00 , G01N33/56938 , G01N2333/31 , G01N2333/78 , G01N2500/00
摘要： Antibodies to the CNA protein and to other regions from the collagen binding domain, including domain CNA19, are provided, and antibodies produced in this manner have been shown to be cross reactive to both Staphylococcus aureus and Staphylococcus epidermidis bacteria and which can thus be used in the prevention and treatment of infections caused by both of these types of bacteria. In addition, medical instruments can be treated using the antibodies of the invention in order to reduce or eliminate the possibility of their becoming infected or further spreading the infection. In particular, the proteins are advantageous because they are cross-reactive and may thus be administered to patients so as to reduce or prevent severe infection by staphylococcal bacteria of more than one species. Antibodies generated in this manner have also been shown to exhibit displacement activity and can thus be utilized advantageously in methods wherein these antibodies will be administered to patients having pre-existing staphylococcal infections because of the ability to displace bacterial proteins from binding sites on the extracellular matrix. Finally, a method of identifying, isolating and utilizing displacing antibodies is also provided.
摘要翻译：提供了对CNA蛋白和来自胶原结合结构域的其他区域（包括结构域CNA19）的抗体，并且以这种方式产生的抗体已显示与金黄色葡萄球菌和表皮葡萄球菌交叉反应，因此可以用于预防和治疗由这两种细菌引起的感染。此外，可以使用本发明的抗体治疗医疗器械，以便减少或消除它们被感染或进一步扩散感染的可能性。特别地，蛋白质是有利的，因为它们是交叉反应性的，并且因此可以施用于患者，以便减少或预防多于一种物种的葡萄球菌细菌的严重感染。以这种方式产生的抗体也已显示出显示置换活性，因此可有利地用于其中将这些抗体施用于具有预先存在的葡萄球菌感染的患者的方法，因为能够从细胞外基质上的结合位点置换细菌蛋白质。最后，还提供了鉴定，分离和利用置换抗体的方法。

3. 发明授权

US07850974B2 Bioinformatic method for identifying surface-anchored proteins from gram-positive bacteria and proteins obtained thereby 有权
标题翻译：用于从革兰氏阳性细菌和由此获得的蛋白质中鉴定表面锚定蛋白的生物信息学方法
公开(公告)号：US07850974B2
公开(公告)日：2010-12-14
申请号：US12575909
申请日：2009-10-08
申请人： Magnus Hook , Yi Xu , Jouko V. Sillanpaa , Narayana Sthanam , Karthe Ponnuraj , Joseph M. Patti , Jeff T. Hutchins , Andrea Hall , Maria G. Bowden
发明人： Magnus Hook , Yi Xu , Jouko V. Sillanpaa , Narayana Sthanam , Karthe Ponnuraj , Joseph M. Patti , Jeff T. Hutchins , Andrea Hall , Maria G. Bowden
IPC分类号： A61K39/02
CPC分类号： G01N33/56916 , A61K38/00 , C07K14/315 , C07K16/1267 , G01N33/56911 , G06F19/16 , G06F19/22 , Y02A90/26 , Y10S435/975
摘要： A bioinformatic method for identifying and isolating proteins and peptides with MSCRAMM®-like characteristics from Gram positive bacteria, such as Enterococcus, Staphylococcus, Streptococcus and Bacillus bacteria, and proteins and peptides obtained thereby are provided which can be utilized in methods to prevent and treat infections caused by Gram-positive bacteria. The method involves identifying from sequence information those proteins with a putative C-terminal LPXTG (SEQ ID NO:1) cell wall sorting signal and other structural similarities to MSCRAMM® proteins having the LPXTG-anchored cell wall proteins. The MSCRAMM® proteins and immunogenic regions therein that are identified and isolated using the present invention may be useful in the diagnosis, treatment or prevention of Gram positive bacterial infections.
摘要翻译：提供了用于从革兰氏阳性细菌如肠球菌属，葡萄球菌属，链球菌属和芽孢杆菌属细菌鉴定和分离具有MSCRAMM®样特征的蛋白质和肽的生物信息学方法，以及由此得到的蛋白质和肽，其可用于预防和治疗革兰氏阳性菌引起的感染。该方法包括从序列信息中鉴定具有推定的C末端LPXTG（SEQ ID NO：1）细胞壁分选信号的蛋白质和具有LPXTG锚定的细胞壁蛋白质的MSCRAMM®蛋白质的其他结构相似性的蛋白质。使用本发明鉴定和分离的MSCRAMM蛋白质及其免疫原性区域可用于革兰氏阳性细菌感染的诊断，治疗或预防。

4. 发明申请

US20100068220A1 BIOINFORMATIC METHOD FOR IDENTIFYING SURFACE-ANCHORED PROTEINS FROM GRAM-POSITIVE BACTERIA AND PROTEINS OBTAINED THEREBY 有权
标题翻译：用于识别表面沉积的蛋白质从生物细菌和蛋白质获得的生物化学方法
公开(公告)号：US20100068220A1
公开(公告)日：2010-03-18
申请号：US12575909
申请日：2009-10-08
申请人： Magnus HOOK , Yi Xu , Jouko V. Sillanpaa , Narayana Sthanam , Karthe Ponnuraj , Joseph M. Patti , Jeff T. Hutchins , Andrea Hall , Maria G. Bowden
发明人： Magnus HOOK , Yi Xu , Jouko V. Sillanpaa , Narayana Sthanam , Karthe Ponnuraj , Joseph M. Patti , Jeff T. Hutchins , Andrea Hall , Maria G. Bowden
IPC分类号： A61K39/085 , C07K14/31 , A61K38/16 , G01N33/53 , A61P31/04 , A61P37/04
CPC分类号： G01N33/56916 , A61K38/00 , C07K14/315 , C07K16/1267 , G01N33/56911 , G06F19/16 , G06F19/22 , Y02A90/26 , Y10S435/975
摘要： A bioinformatic method for identifying and isolating proteins and peptides with MSCRAMM®-like characteristics from Gram positive bacteria, such as Enterococcus, Staphylococcus, Streptococcus and Bacillus bacteria, and proteins and peptides obtained thereby are provided which can be utilized in methods to prevent and treat infections caused by Gram-positive bacteria. The method involves identifying from sequence information those proteins with a putative C-terminal LPXTG (SEQ ID NO:1) cell wall sorting signal and other structural similarities to MSCRAMM® proteins having the LPXTG-anchored cell wall proteins. The MSCRAMM® proteins and immunogenic regions therein that are identified and isolated using the present invention may be useful in the diagnosis, treatment or prevention of Gram positive bacterial infections.
摘要翻译：提供了用于从革兰氏阳性细菌如肠球菌属，葡萄球菌属，链球菌属和芽孢杆菌属细菌鉴定和分离具有MSCRAMM®样特征的蛋白质和肽的生物信息学方法，以及由此得到的蛋白质和肽，其可用于预防和治疗革兰氏阳性菌引起的感染。该方法包括从序列信息中鉴定具有推定的C末端LPXTG（SEQ ID NO：1）细胞壁分选信号的蛋白质和具有LPXTG锚定的细胞壁蛋白质的MSCRAMM®蛋白质的其他结构相似性的蛋白质。使用本发明鉴定和分离的MSCRAMM蛋白质及其免疫原性区域可用于革兰氏阳性细菌感染的诊断，治疗或预防。

5. 发明授权

US07615616B2 Bioinformatic method for identifying surface-anchored proteins from gram-positive bacteria and proteins obtained thereby 有权
标题翻译：用于从革兰氏阳性细菌和由此获得的蛋白质中鉴定表面锚定蛋白的生物信息学方法
公开(公告)号：US07615616B2
公开(公告)日：2009-11-10
申请号：US10661809
申请日：2003-09-15
申请人： Magnus Hook , Yi Xu , Jouko V. Sillanpaa , Narayana Sthanam , Karthe Ponnuraj , Joseph M. Patti , Jeff T. Hutchins , Andrea Hall , Maria G. Bowden
发明人： Magnus Hook , Yi Xu , Jouko V. Sillanpaa , Narayana Sthanam , Karthe Ponnuraj , Joseph M. Patti , Jeff T. Hutchins , Andrea Hall , Maria G. Bowden
IPC分类号： C07K16/00
CPC分类号： G01N33/56916 , A61K38/00 , C07K14/315 , C07K16/1267 , G01N33/56911 , G06F19/16 , G06F19/22 , Y02A90/26 , Y10S435/975
摘要： A bioinformatic method is provided for identifying and isolating proteins with MSCRAMM®—like characteristics from Gram positive bacteria, such as Enterococcus, Staphylococcus, Streptococcus and Bacillus bacteria, which can then be utilized in methods to prevent and treat infections caused by Gram-positive bacteria. The method involves identifying from sequence information those proteins with a putative C-terminal LPXTG (SEQ ID NO:1) cell wall sorting signal and other structural similarities to MSCRAMM® proteins having the LPXTG-anchored cell wall proteins. The MSCRAMM® proteins and immunogenic regions therein that are identified and isolated using the present invention may be used to generate antibodies useful in the diagnosis, treatment or prevention of Gram positive bacterial infections.
摘要翻译：提供了一种生物信息学方法，用于从革兰氏阳性菌（例如肠球菌属，葡萄球菌属，链球菌属和芽孢杆菌属细菌）中鉴定和分离具有类似MSCRAMM（R）样特征的蛋白质，其可用于预防和治疗由革兰氏阴性菌引起的感染的方法，阳性细菌。该方法包括从序列信息中鉴定具有推定的C末端LPXTG（SEQ ID NO：1）细胞壁分选信号的蛋白质和具有LPXTG锚定的细胞壁蛋白质的MSCRAMM蛋白质的其它结构相似性的蛋白质。使用本发明鉴定和分离的MSCRAMM蛋白质及其免疫原性区域可用于产生用于诊断，治疗或预防革兰氏阳性细菌感染的抗体。

6. 发明申请

US20050002925A1 Surface proteins from gram-positive bacteria having highly conserved motifs and antibodies that recognize them 失效
标题翻译：来自具有高度保守基序的革兰氏阳性细菌的表面蛋白和识别它们的抗体
公开(公告)号：US20050002925A1
公开(公告)日：2005-01-06
申请号：US10911507
申请日：2004-08-05
申请人： Yi Xu , Magnus Hook
发明人： Yi Xu , Magnus Hook
IPC分类号： A61K39/00 , C07K14/31 , C07K14/315 , C07K16/12 , A61K39/395
CPC分类号： C07K14/3156 , A61K39/00 , A61K2039/505 , C07K14/31 , C07K14/315 , C07K16/1267 , Y10S930/29
摘要： Isolated peptide sequences and proteins containing these sequences are provided which are useful in the prevention and treatment of infection caused by Gram-positive bacteria. The peptide sequences have been shown to be highly conserved motifs in the surface proteins of Gram-positive bacteria, and these consensus sequences include amino acid sequences such as LPXTG (SEQ ID NO:13), ALKTGKIDIIISGMTSTPERKK (SEQ ID NO:14), VEGAVVEKPVAEAYLKQN (SEQ ID NO:15), and EYAGVDIDLAKKIAK (SEQ ID NO:16). By virtue of the highly conserved regions, the sequences and the proteins including these sequences can be utilized to generate antibodies which can recognize these highly conserved motifs and the proteins containing them and thus be useful in the treatment or prevention of a wide range of infections caused by Gram-positive bacteria.
摘要翻译：提供了含有这些序列的分离的肽序列和蛋白质，其可用于预防和治疗由革兰氏阳性菌引起的感染。已经显示肽序列在革兰氏阳性细菌的表面蛋白中是高度保守的基序，并且这些共有序列包括氨基酸序列，例如LPXTG（SEQ ID NO：13），ALKTGKIDIIISGMTSTPERKK（SEQ ID NO：14），VEGAVVEKPVAEAYLKQN （SEQ ID NO：15）和EYAGVDIDLAKKIAK（SEQ ID NO：16）。由于高度保守的区域，包括这些序列的序列和蛋白质可用于产生能识别这些高度保守的基序和含有它们的蛋白质的抗体，因此可用于治疗或预防引起的广泛感染通过革兰氏阳性菌。

7. 发明申请

US20090258390A1 Prokaryotic collagen-like proteins and uses thereof 有权
标题翻译：原核胶原蛋白及其用途
公开(公告)号：US20090258390A1
公开(公告)日：2009-10-15
申请号：US12455840
申请日：2009-06-08
申请人： Magnus Hook , Slawomir Lukomski , Yi Xu
发明人： Magnus Hook , Slawomir Lukomski , Yi Xu
IPC分类号： C12P21/02 , C12N1/21 , C12N15/63 , G01N33/566 , C07K14/78 , C07K16/12
CPC分类号： C07K14/78
摘要： The present invention provides recombinant triple helical proteins or collagen-like proteins comprising a prokaryotic protein or one or more domains of a prokaryotic protein comprising a collagen-like peptide sequence of repeated Gly-Xaa-Yaa triplets and, optionally, one or more domains from a mammalian collagen. Also provided are expression vectors and host cells containing the expression vectors to produce these recombinant proteins and methods of producing the same. Additionally, antibodies are provided that are directed against a recombinant collagen-like protein that, preferably, binds an integrin. Furthermore, a method of screening for potential therapeutic compounds that inhibit the integrin-binding or integrin-interacting activities of recombinant collagen-like proteins.
摘要翻译：本发明提供重组三螺旋蛋白或胶原样蛋白，其包含原核蛋白或原核蛋白的一个或多个结构域，其包含重复Gly-Xaa-Yaa三联体的胶原样肽序列和任选的一个或多个结构域哺乳动物胶原蛋白。还提供了含有表达载体以产生这些重组蛋白的表达载体和宿主细胞及其生产方法。此外，提供针对重组胶原样蛋白的抗体，其优选结合整联蛋白。此外，筛选抑制重组胶原样蛋白的整联蛋白结合或整联蛋白相互作用活性的潜在治疗化合物的方法。

8. 发明申请

US20080014613A1 Prokaryotic collagen-like proteins and uses thereof 有权
标题翻译：原核胶原蛋白及其用途
公开(公告)号：US20080014613A1
公开(公告)日：2008-01-17
申请号：US11800288
申请日：2007-05-04
申请人： Magnus Hook , Slawomir Lukomski , Yi Xu
发明人： Magnus Hook , Slawomir Lukomski , Yi Xu
IPC分类号： C12P21/00 , C07K14/78 , C07K16/12 , C12N1/00 , G01N33/00 , C12N1/21 , C12N15/63
CPC分类号： C07K14/78
摘要： The present invention provides recombinant triple helical proteins or collagen-like proteins comprising a prokaryotic protein or one or more domains of a prokaryotic protein comprising a collagen-like peptide sequence of repeated Gly-Xaa-Yaa triplets and, optionally, one or more domains from a mammalian collagen. Also provided are expression vectors and host cells containing the expression vectors to produce these recombinant proteins and methods of production for the same. Additionally, antibodies are provided that are directed against a recombinant collagen-like protein that, preferably, binds an integrin. Furthermore, a method of screening for potential therapeutic compounds that inhibit the integrin-binding or -interacting activities of recombinant collagen-like proteins.
摘要翻译：本发明提供重组三螺旋蛋白或胶原样蛋白，其包含原核蛋白或原核蛋白的一个或多个结构域，其包含重复Gly-Xaa-Yaa三联体的胶原样肽序列和任选的一个或多个结构域哺乳动物胶原蛋白。还提供了含有表达载体以产生这些重组蛋白的表达载体和宿主细胞及其生产方法。此外，提供针对重组胶原样蛋白的抗体，其优选结合整联蛋白。此外，筛选抑制重组胶原样蛋白的整联蛋白结合或相互作用活性的潜在治疗化合物的方法。

9. 发明申请

US20060035336A1 Prokaryotic collagen-like proteins and uses thereof 有权
公开(公告)号：US20060035336A1
公开(公告)日：2006-02-16
申请号：US11245689
申请日：2005-10-07
申请人： Magnus Hook , Slawomir Lukomski , Yi Xu
发明人： Magnus Hook , Slawomir Lukomski , Yi Xu
IPC分类号： C07H21/04 , C12P21/06 , C12N1/21
CPC分类号： C07H21/04 , C07K14/315 , C07K14/78
摘要： The present invention provides recombinant triple helical proteins or collagen-like proteins comprising a prokaryotic protein or one or more domains of a prokaryotic protein comprising a collagen-like peptide sequence of repeated Gly-Xaa-Yaa triplets and, optionally, one or more domains from a mammalian collagen. Also provided are expression vectors and host cells containing the expression vectors to produce these recombinant proteins and methods of production for the same. Additionally, antibodies are provided that are directed against a recombinant collagen-like protein that, preferably, binds an integrin. Furthermore, a method of screening for potential therapeutic compounds that inhibit the integrin-binding or -interacting activities of recombinant collagen-like proteins.

10. 发明申请

US20060198852A1 Collagen-binding MSCRAMMs of Bacillus anthracis and uses therefor 审中-公开
标题翻译：炭疽芽孢杆菌的胶原结合MSCRAMM并用于此
公开(公告)号：US20060198852A1
公开(公告)日：2006-09-07
申请号：US11158163
申请日：2005-06-21
申请人： Magnus Hook , Yi Xu
发明人： Magnus Hook , Yi Xu
IPC分类号： C07K14/32 , C12N1/21 , C07H21/04 , C12N15/74 , A61K39/02
CPC分类号： C07K14/32 , A61K39/00 , A61K2039/53
摘要： The present invention provides cell wall anchored proteins of Bacillus anthracis representative of the MSCRAMM family of proteins and DNAs encoding the same. Also provided are collagen-binding peptides comprising the collagen-binding region A of the cell wall anchored proteins and DNAs encoding these peptides. Further provided are pharmaceutical compositions and immunogenic compositions thereof the cell wall anchored proteins, collagen-binding peptides and encoding DNAs. The immunogenic compositions are useful in methods of inducing an immune response against Bacillus anthracis.
摘要翻译：本发明提供代表MSCRAMM家族蛋白质的炭疽芽孢杆菌的细胞壁锚定蛋白和编码它们的DNA。还提供了包含细胞壁锚定蛋白的胶原结合区域A和编码这些肽的DNA的胶原结合肽。还提供了细胞壁锚定蛋白，胶原结合肽和编码DNA的药物组合物及其免疫原性组合物。免疫原性组合物可用于诱导针对炭疽杆菌的免疫应答的方法。

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