公开(公告)号：US20120149061A1

公开(公告)日：2012-06-14

申请号：US13315623

申请日：2011-12-09

申请人： NANCY E. STAGLIANO ,  JAMES W. WEST ,  KATHRYN KAMATH ,  PAUL H. BESSETTE ,  FREDERICK W. GLUCK ,  JASON SAGERT ,  PATRICK DAUGHERTY

发明人： NANCY E. STAGLIANO ,  JAMES W. WEST ,  KATHRYN KAMATH ,  PAUL H. BESSETTE ,  FREDERICK W. GLUCK ,  JASON SAGERT ,  PATRICK DAUGHERTY

IPC分类号： C12P21/00 ,  C07K16/00

CPC分类号： C07K16/22 ,  A61K39/3955 ,  A61K47/6845 ,  A61K47/6849 ,  A61K2039/505 ,  A61K2039/507 ,  C07K7/06 ,  C07K7/08 ,  C07K14/001 ,  C07K16/00 ,  C07K16/18 ,  C07K16/241 ,  C07K16/28 ,  C07K16/2818 ,  C07K16/2845 ,  C07K16/2863 ,  C07K16/2866 ,  C07K16/2875 ,  C07K16/2896 ,  C07K16/30 ,  C07K2317/20 ,  C07K2317/21 ,  C07K2317/34 ,  C07K2317/40 ,  C07K2317/51 ,  C07K2317/515 ,  C07K2317/52 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/622 ,  C07K2317/92 ,  C07K2317/94 ,  C07K2319/30 ,  C07K2319/31 ,  C07K2319/50 ,  G01N33/6845 ,  G01N33/6854

摘要： The present disclosure provides modified antibodies which contain an antibody or antibody fragment (AB) modified with a masking moiety (MM). Such modified antibodies can be further coupled to a cleavable moiety (CM), resulting in activatable antibodies (AAs), wherein the CM is capable of being cleaved, reduced, photolysed, or otherwise modified. AAs can exhibit an activatable conformation such that the AB is more accessible to a target after, for example, removal of the MM by cleavage, reduction, or photolysis of the CM in the presence of an agent capable of cleaving, reducing, or photolysing the CM. The disclosure further provides methods of making and using such modified antibodies and activatable antibodies.

公开(公告)号：US20070065878A1

公开(公告)日：2007-03-22

申请号：US11514377

申请日：2006-08-30

申请人： Patrick Daugherty ,  Kevin Boulware

发明人： Patrick Daugherty ,  Kevin Boulware

IPC分类号： C40B30/06 ,  C40B40/02

CPC分类号： C12N15/1044 ,  C07K14/245 ,  C07K2319/03 ,  C07K2319/22 ,  C07K2319/60 ,  C12N15/1037 ,  C12Q1/37 ,  C40B40/02 ,  C40B40/10 ,  G01N21/6486

摘要： The present invention provides compositions including peptide display scaffolds that present at least one candidate peptide and at least one detectable moiety in at least one of the N-terminal and C-terminal candidate peptide presenting domains that when expressed in a cell are accessible at a surface of the cell outermembrane. In addition, the present invention also provides kits and methods for screening a library of cells presenting the candidate peptides in peptide display scaffolds to identify a ligand for an enzyme.

摘要翻译： 本发明提供了包含肽显示支架的组合物，其在至少一个N-末端和C-末端候选肽呈递区域中呈现至少一个候选肽和至少一个可检测部分，当在细胞中表达时， 的细胞外膜。 此外，本发明还提供了用于筛选在肽展示支架中呈现候选肽的细胞文库以鉴定酶的配体的试剂盒和方法。

公开(公告)号：US5699982A

公开(公告)日：1997-12-23

申请号：US506163

申请日：1995-07-24

申请人： Joseph Patrick Daugherty

发明人： Joseph Patrick Daugherty

IPC分类号： B64G1/50

CPC分类号： B64G1/503 ,  B64G1/50

摘要： A spacecraft includes heat-radiating panels. Heat-generating boxes such as TWTs are mounted on shelves which are inside the spacecraft, where they cannot radiate to space. The shelves are coupled by bent heat pipes to the exterior radiating panels.

摘要翻译： 航天器包括散热板。 诸如TWT的发热箱安装在飞船内的货架上，在那里它们不能辐射到太空。 货架通过弯曲的热管连接到外部散热板。

公开(公告)号：US08513390B2

公开(公告)日：2013-08-20

申请号：US13455924

申请日：2012-04-25

申请人： Nancy E. Stagliano ,  James W. West ,  Kathryn Kamath ,  Paul H. Bessette ,  Fred Gluck ,  Jason Sagert ,  Patrick Daugherty

发明人： Nancy E. Stagliano ,  James W. West ,  Kathryn Kamath ,  Paul H. Bessette ,  Fred Gluck ,  Jason Sagert ,  Patrick Daugherty

IPC分类号： C07K16/28 ,  C07K14/00 ,  C07K16/46 ,  A61K39/00 ,  A61K38/10 ,  A61K38/08

CPC分类号： C07K16/22 ,  A61K39/3955 ,  A61K47/6845 ,  A61K47/6849 ,  A61K2039/505 ,  A61K2039/507 ,  C07K7/06 ,  C07K7/08 ,  C07K14/001 ,  C07K16/00 ,  C07K16/18 ,  C07K16/241 ,  C07K16/28 ,  C07K16/2818 ,  C07K16/2845 ,  C07K16/2863 ,  C07K16/2866 ,  C07K16/2875 ,  C07K16/2896 ,  C07K16/30 ,  C07K2317/20 ,  C07K2317/21 ,  C07K2317/34 ,  C07K2317/40 ,  C07K2317/51 ,  C07K2317/515 ,  C07K2317/52 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/622 ,  C07K2317/92 ,  C07K2317/94 ,  C07K2319/30 ,  C07K2319/31 ,  C07K2319/50 ,  G01N33/6845 ,  G01N33/6854

摘要： The present disclosure provides modified antibodies which contain an antibody or antibody fragment (AB) modified with a masking moiety (MM). Such modified antibodies can be further coupled to a cleavable moiety (CM), resulting in activatable antibodies (AAs), wherein the CM is capable of being cleaved, reduced, photolysed, or otherwise modified. AAs can exhibit an activatable conformation such that the AB is more accessible to a target after, for example, removal of the MM by cleavage, reduction, or photolysis of the CM in the presence of an agent capable of cleaving, reducing, or photolysing the CM. The disclosure further provides methods of making and using such modified antibodies and activatable antibodies.

公开(公告)号：US20120244154A1

公开(公告)日：2012-09-27

申请号：US13411409

申请日：2012-03-02

申请人： Patrick Daugherty ,  Nancy Stagliano ,  Jerry Thomas ,  Kathryn Kamath ,  James W. West ,  Sanjay Khare

发明人： Patrick Daugherty ,  Nancy Stagliano ,  Jerry Thomas ,  Kathryn Kamath ,  James W. West ,  Sanjay Khare

IPC分类号： C07K19/00 ,  C12P21/02 ,  C12N15/63 ,  A61K39/395 ,  C12N15/62

CPC分类号： C07K16/22 ,  C07K16/24 ,  C07K16/2818 ,  C07K16/2836 ,  C07K16/42 ,  C07K2317/34 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/30 ,  C07K2319/50 ,  C12N15/1034 ,  C12N15/1044

摘要： Activatable binding polypeptides (ABPs), which contain a target binding moiety (TBM), a masking moiety (MM), and a cleavable moiety (CM) are provided. Activatable antibody compositions, which contain a TBM containing an antigen binding domain (ABD), a MM and a CM are provided. Furthermore, ABPs which contain a first TBM, a second TBM and a CM are provided. The ABPs exhibit an “activatable” conformation such that at least one of the TBMs is less accessible to target when uncleaved than after cleavage of the CM in the presence of a cleaving agent capable of cleaving the CM. Further provided are libraries of candidate ABPs, methods of screening to identify such ABPs, and methods of use. Further provided are ABPs having TBMs that bind VEGF, CTLA-4, or VCAM, ABPs having a first TBM that binds VEGF and a second TBM that binds FGF, as well as compositions and methods of use.

公开(公告)号：US20120207756A1

公开(公告)日：2012-08-16

申请号：US13455924

申请日：2012-04-25

申请人： Nancy E. Stagliano ,  James W. West ,  Kathryn Kamath ,  Paul H. Bessette ,  Frederick W. Gluck ,  Jason Sagert ,  Patrick Daugherty

发明人： Nancy E. Stagliano ,  James W. West ,  Kathryn Kamath ,  Paul H. Bessette ,  Frederick W. Gluck ,  Jason Sagert ,  Patrick Daugherty

IPC分类号： A61K39/395 ,  A61P35/00 ,  A61P9/00 ,  C07K1/107 ,  C12N15/63 ,  C12P21/00 ,  C12P21/02 ,  C12N15/62 ,  C07K19/00

CPC分类号： C07K16/22 ,  A61K39/3955 ,  A61K47/6845 ,  A61K47/6849 ,  A61K2039/505 ,  A61K2039/507 ,  C07K7/06 ,  C07K7/08 ,  C07K14/001 ,  C07K16/00 ,  C07K16/18 ,  C07K16/241 ,  C07K16/28 ,  C07K16/2818 ,  C07K16/2845 ,  C07K16/2863 ,  C07K16/2866 ,  C07K16/2875 ,  C07K16/2896 ,  C07K16/30 ,  C07K2317/20 ,  C07K2317/21 ,  C07K2317/34 ,  C07K2317/40 ,  C07K2317/51 ,  C07K2317/515 ,  C07K2317/52 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/622 ,  C07K2317/92 ,  C07K2317/94 ,  C07K2319/30 ,  C07K2319/31 ,  C07K2319/50 ,  G01N33/6845 ,  G01N33/6854

摘要： The present disclosure provides modified antibodies which contain an antibody or antibody fragment (AB) modified with a masking moiety (MM). Such modified antibodies can be further coupled to a cleavable moiety (CM), resulting in activatable antibodies (AAs), wherein the CM is capable of being cleaved, reduced, photolysed, or otherwise modified. AAs can exhibit an activatable conformation such that the AB is more accessible to a target after, for example, removal of the MM by cleavage, reduction, or photolysis of the CM in the presence of an agent capable of cleaving, reducing, or photolysing the CM. The disclosure further provides methods of making and using such modified antibodies and activatable antibodies.

摘要翻译： 本公开提供了修饰的抗体，其含有用掩蔽部分（MM）修饰的抗体或抗体片段（AB）。 这样的修饰抗体可以进一步与可切割部分（CM）偶联，产生可激活抗体（AAs），其中CM能够被切割，还原，光解或以其它方式修饰。 AAs可以表现出可激活的构象，使得AB在例如通过在能够切割，还原或光解所述蛋白质的试剂存在下，通过CM的切割，还原或光解来除去MM来更容易地进行靶标 厘米。 本公开进一步提供了制备和使用这些修饰抗体和可激活抗体的方法。

公开(公告)号：US20090304719A1

公开(公告)日：2009-12-10

申请号：US12196269

申请日：2008-08-21

申请人： Patrick Daugherty ,  Nancy Stagliano ,  Jerry Thomas ,  Kathryn Kamath ,  James W. West ,  Sanjay Khare

发明人： Patrick Daugherty ,  Nancy Stagliano ,  Jerry Thomas ,  Kathryn Kamath ,  James W. West ,  Sanjay Khare

IPC分类号： A61K39/395 ,  C07K2/00 ,  C07K14/00 ,  C40B30/04 ,  C40B40/10 ,  C40B40/02 ,  C12N15/11 ,  C40B50/06 ,  A61K38/16 ,  C12P21/06 ,  G01N33/53 ,  C07K16/00 ,  A61K49/00 ,  C12N9/68 ,  C12N9/50

CPC分类号： C07K16/22 ,  C07K16/24 ,  C07K16/2818 ,  C07K16/2836 ,  C07K16/42 ,  C07K2317/34 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/30 ,  C07K2319/50 ,  C12N15/1034 ,  C12N15/1044

摘要： The present disclosure provides activatable binding polypeptides (ABPs), which contain a target binding moiety (TBM), a masking moiety (MM), and a cleavable moiety (CM). The present disclosure provides activatable antibody compositions, which contain a TBM containing an antigen binding domain (ABD), a MM and a CM. Furthermore the present disclosure also provides ABPs which contain a first TBM, a second TBM and a CM. The ABPs exhibit an “activatable” conformation such that at least one of the TBMs is less accessible to target when uncleaved than after cleavage of the CM in the presence of a cleaving agent capable of cleaving the CM. The disclosure further provides libraries of candidate ABPs, methods of screening to identify such ABPs, and methods of use. The disclosure further provides ABPs having TBMs that bind VEGF, CTLA-4, or VCAM, ABPs having a first TBM that binds VEGF and a second TBM that binds FGF, as well as compositions and methods of use.

摘要翻译： 本公开提供了可激活的结合多肽（ABP），其包含靶结合部分（TBM），掩蔽部分（MM）和可切割部分（CM）。 本公开提供可激活的抗体组合物，其含有含有抗原结合结构域（ABD），MM和CM的TBM。 此外，本公开还提供了包含第一TBM，第二TBM和CM的ABP。 ABP表现出“可激活”构象，使得当不能切割CM时，在存在能够切割CM的切割剂的情况下，TBM中的至少一种在未切割时难以接触。 本公开进一步提供候选ABP的文库，筛选鉴定这种ABP的方法和使用方法。 本公开进一步提供了具有结合VEGF，CTLA-4或VCAM，具有结合VEGF的第一TBM的ABP和结合FGF的第二TBM的TBM以及组合物和使用方法的ABP。

公开(公告)号：US08563269B2

公开(公告)日：2013-10-22

申请号：US13315623

申请日：2011-12-09

申请人： Nancy E. Stagliano ,  James W. West ,  Kathryn Kamath ,  Paul H. Bessette ,  Frederick W. Gluck ,  Jason Sagert ,  Patrick Daugherty

发明人： Nancy E. Stagliano ,  James W. West ,  Kathryn Kamath ,  Paul H. Bessette ,  Frederick W. Gluck ,  Jason Sagert ,  Patrick Daugherty

IPC分类号： C12P21/08 ,  C12N15/74 ,  C12N9/00 ,  C12N15/62 ,  C07H21/04 ,  C07K16/28 ,  C07K16/46 ,  C07K14/00

CPC分类号： C07K16/22 ,  A61K39/3955 ,  A61K47/6845 ,  A61K47/6849 ,  A61K2039/505 ,  A61K2039/507 ,  C07K7/06 ,  C07K7/08 ,  C07K14/001 ,  C07K16/00 ,  C07K16/18 ,  C07K16/241 ,  C07K16/28 ,  C07K16/2818 ,  C07K16/2845 ,  C07K16/2863 ,  C07K16/2866 ,  C07K16/2875 ,  C07K16/2896 ,  C07K16/30 ,  C07K2317/20 ,  C07K2317/21 ,  C07K2317/34 ,  C07K2317/40 ,  C07K2317/51 ,  C07K2317/515 ,  C07K2317/52 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/622 ,  C07K2317/92 ,  C07K2317/94 ,  C07K2319/30 ,  C07K2319/31 ,  C07K2319/50 ,  G01N33/6845 ,  G01N33/6854

摘要： The present disclosure provides modified antibodies which contain an antibody or antibody fragment (AB) modified with a masking moiety (MM). Such modified antibodies can be further coupled to a cleavable moiety (CM), resulting in activatable antibodies (AAs), wherein the CM is capable of being cleaved, reduced, photolysed, or otherwise modified. AAs can exhibit an activatable conformation such that the AB is more accessible to a target after, for example, removal of the MM by cleavage, reduction, or photolysis of the CM in the presence of an agent capable of cleaving, reducing, or photolysing the CM. The disclosure further provides methods of making and using such modified antibodies and activatable antibodies.

摘要翻译： 本公开提供了修饰的抗体，其含有用掩蔽部分（MM）修饰的抗体或抗体片段（AB）。 这样的修饰抗体可以进一步与可切割部分（CM）偶联，产生可激活抗体（AAs），其中CM能够被切割，还原，光解或以其它方式修饰。 AAs可以表现出可激活的构象，使得AB在例如通过在能够切割，还原或光解所述蛋白质的试剂存在下，通过CM的切割，还原或光解来除去MM来更容易地进行靶标 厘米。 本公开进一步提供了制备和使用这些修饰抗体和可激活抗体的方法。

公开(公告)号：US08518404B2

公开(公告)日：2013-08-27

申请号：US13411409

申请日：2012-03-02

申请人： Patrick Daugherty ,  Nancy Stagliano ,  Jerry Thomas ,  Kathryn Kamath ,  James W. West ,  Sanjay Khare ,  Jason Sagert

发明人： Patrick Daugherty ,  Nancy Stagliano ,  Jerry Thomas ,  Kathryn Kamath ,  James W. West ,  Sanjay Khare ,  Jason Sagert

IPC分类号： A61K39/00 ,  A61K39/395 ,  C07K16/28 ,  C07K16/46

CPC分类号： C07K16/22 ,  C07K16/24 ,  C07K16/2818 ,  C07K16/2836 ,  C07K16/42 ,  C07K2317/34 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/30 ,  C07K2319/50 ,  C12N15/1034 ,  C12N15/1044

摘要： Activatable binding polypeptides (ABPs), which contain a target binding moiety (TBM), a masking moiety (MM), and a cleavable moiety (CM) are provided. Activatable antibody compositions, which contain a TBM containing an antigen binding domain (ABD), a MM and a CM are provided. Furthermore, ABPs which contain a first TBM, a second TBM and a CM are provided. The ABPs exhibit an “activatable” conformation such that at least one of the TBMs is less accessible to target when uncleaved than after cleavage of the CM in the presence of a cleaving agent capable of cleaving the CM. Further provided are libraries of candidate ABPs, methods of screening to identify such ABPs, and methods of use. Further provided are ABPs having TBMs that bind VEGF, CTLA-4, or VCAM, ABPs having a first TBM that binds VEGF and a second TBM that binds FGF, as well as compositions and methods of use.

摘要翻译： 提供了含有靶结合部分（TBM），掩蔽部分（MM）和可切割部分（CM）的可活化结合多肽（ABPs）。 提供含有含有抗原结合结构域（ABD），MM和CM的TBM的可活化抗体组合物。 此外，提供了包含第一TBM，第二TBM和CM的ABP。 ABP表现出“可激活”构象，使得当不能切割CM时，在存在能够切割CM的切割剂的情况下，TBM中的至少一种在未切割时难以接触。 还提供了候选ABP的图书馆，筛选鉴定这种ABP的方法和使用方法。 还提供了具有结合VEGF，CTLA-4或VCAM的TBM的ABP，具有结合VEGF的第一TBM的ABP和结合FGF的第二TBM，以及组合物和使用方法。

公开(公告)号：US20120237977A1

公开(公告)日：2012-09-20

申请号：US13411416

申请日：2012-03-02

申请人： Patrick Daugherty ,  Nancy Stagliano ,  Jerry Thomas ,  Kathryn Kamath ,  James W. West ,  Sanjay Khare

发明人： Patrick Daugherty ,  Nancy Stagliano ,  Jerry Thomas ,  Kathryn Kamath ,  James W. West ,  Sanjay Khare

IPC分类号： C07K19/00 ,  C12P21/08 ,  C12P21/00

CPC分类号： C07K16/22 ,  C07K16/24 ,  C07K16/2818 ,  C07K16/2836 ,  C07K16/42 ,  C07K2317/34 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/30 ,  C07K2319/50 ,  C12N15/1034 ,  C12N15/1044

摘要： Activatable binding polypeptides (ABPs), which contain a target binding moiety (TBM), a masking moiety (MM), and a cleavable moiety (CM) are provided. Activatable antibody compositions, which contain a TBM containing an antigen binding domain (ABD), a MM and a CM are provided. Furthermore, ABPs which contain a first TBM, a second TBM and a CM are provided. The ABPs exhibit an “activatable” conformation such that at least one of the TBMs is less accessible to target when uncleaved than after cleavage of the CM in the presence of a cleaving agent capable of cleaving the CM. Further provided are libraries of candidate ABPs, methods of screening to identify such ABPs, and methods of use. Further provided are ABPs having TBMs that bind VEGF, CTLA-4, or VCAM, ABPs having a first TBM that binds VEGF and a second TBM that binds FGF, as well as compositions and methods of use.