公开(公告)号：US20110171285A1

公开(公告)日：2011-07-14

申请号：US12914511

申请日：2010-10-28

申请人： MAGNUS HOOK ,  VANNAKAMBADI K. GANESH ,  EMANUEL SMEDS

发明人： MAGNUS HOOK ,  VANNAKAMBADI K. GANESH ,  EMANUEL SMEDS

IPC分类号： A61K38/48 ,  C07K14/435 ,  A61K8/64 ,  A61L15/32 ,  A61Q17/04 ,  A61P17/02 ,  A61P7/04 ,  A61P31/00 ,  A61P31/12 ,  A61P31/10 ,  A61P29/00 ,  A61P23/02 ,  A61K9/14 ,  A61K9/00 ,  C07H21/04 ,  C12N15/63

CPC分类号： C07K14/75 ,  A61F2/24 ,  A61K38/00 ,  A61L15/32 ,  A61L15/44 ,  A61L15/46 ,  A61L26/0042 ,  A61L27/227 ,  A61L27/34 ,  A61M5/178 ,  A61M2205/0205 ,  A61M2205/0238

摘要： The present invention describes the design and development of new fibrinogen and fibrinogen derived products with significantly reduced binding to bacteria while retaining normal physiological functions by using modified fibrinogen amino acid sequences. The present invention describes modified sequences of Fg γ-chains and β-chains with reduced binding to S. aureus ClfA and S. epidermidis SdrG respectively. Modified Fg with the described modifications will not bind other bacterial surface proteins that bind Fg using similar mechanisms as ClfA and SdrG. These new Fg and Fg derived products will therefore have less binding to bacteria and will be advantageous compared to normal human Fg in a number of different settings.

摘要翻译： 本发明描述了新的纤维蛋白原和纤维蛋白原衍生产物的设计和开发，其具有显着降低的结​​合细菌，同时通过使用改良的纤维蛋白原氨基酸序列保持正常的生理功能。 本发明分别描述了与金黄色葡萄球菌ClfA和表皮葡萄球菌SdrG结合降低的Fgγ-链和“链”链的修饰序列。 具有所述修饰的修饰的Fg将不会使用与ClfA和SdrG类似的机制结合结合Fg的其它细菌表面蛋白。 因此，这些新的Fg和Fg衍生产品对细菌的结合较少，并且与许多不同设置中的正常人Fg相比将是有利的。

公开(公告)号：US20130035476A1

公开(公告)日：2013-02-07

申请号：US13605567

申请日：2012-09-06

申请人： Magnus Hook ,  Ya-Ping Ko ,  Emanuel Smeds ,  Vannakambadi K. Ganesh

发明人： Magnus Hook ,  Ya-Ping Ko ,  Emanuel Smeds ,  Vannakambadi K. Ganesh

IPC分类号： C07K16/12

CPC分类号： C07K14/75 ,  A61K38/00 ,  A61K38/363 ,  C07K14/31 ,  C07K16/1271 ,  C07K16/18 ,  C07K16/36 ,  G01N33/68 ,  G01N2333/31 ,  G01N2333/75

摘要： The present invention discloses crystal structure of Staphylococcus aureus Clumping factor A (ClfA) in complex with fibrinogen (Fg) derived peptide. Also, the present invention also discloses the use of this structure in the design of ClfA targeted vaccines and therapeutic agents (including monoclonal antibodies). In addition, the present invention discloses isolated and purified engineered Staphylococcus clumping factor A protein (ClfA) with a stabilized, closed conformation and immunogenic compositions thereof including methods of treating a Staphylococcus infection in an individual.

公开(公告)号：US08280643B2

公开(公告)日：2012-10-02

申请号：US12459327

申请日：2009-06-30

申请人： Magnus Hook ,  Ya-Ping Ko ,  Emanuel Smeds ,  Vannakambadi K. Ganesh

发明人： Magnus Hook ,  Ya-Ping Ko ,  Emanuel Smeds ,  Vannakambadi K. Ganesh

IPC分类号： G06F19/00 ,  G01N31/00

CPC分类号： C07K14/75 ,  A61K38/00 ,  A61K38/363 ,  C07K14/31 ,  C07K16/1271 ,  C07K16/18 ,  C07K16/36 ,  G01N33/68 ,  G01N2333/31 ,  G01N2333/75

摘要： The present invention provides a method for determining the structure of a microbial surface components recognizing adhesive matrix molecule in complex with fibrinogen, by providing a ClfA complexed with a fibrinogen gamma-peptide; determining a ClfA binding region of the fibrinogen gamma-peptide; determining one or more critical amino acid residues in the ClfA binding region of a native fibrinogen gamma-peptide that is critical for a ClfA:fibrinogen gamma-peptide interaction; determining one or more amino acid residues of the ClfA that binds to the ClfA binding region of the native fibrinogen gamma-peptide; modeling the structure of the ClfA binding region; determining the structure of the ClfA in complex with the :fibrinogen gamma-peptide interaction; and identifying one or more potential agent(s) that inhibit the ClfA:fibrinogen gamma-peptide interaction without affecting binding of other proteins to the fibrinogen gamma-peptide.

摘要翻译： 本发明提供了一种通过提供与纤维蛋白原γ肽复合的ClfA来确定识别与纤维蛋白原复合的粘合剂基质分子的微生物表面成分的结构的方法; 测定纤维蛋白原γ肽的ClfA结合区域; 确定对ClfA：纤维蛋白原γ-肽相互作用至关重要的天然纤维蛋白原γ-肽的ClfA结合区域中的一个或多个关键氨基酸残基; 确定与天然纤维蛋白原γ肽的ClfA结合区结合的ClfA的一个或多个氨基酸残基; 建模ClfA结合区域的结构; 确定与纤维蛋白原γ-肽相互作用复合的ClfA的结构; 以及鉴定抑制ClfA：纤维蛋白原γ-肽相互作用的一种或多种潜在药剂，而不影响其它蛋白质与纤维蛋白原γ-肽的结合。