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1. 发明授权

US08399219B2 Protease activatable interferon alpha proprotein 有权
标题翻译：蛋白酶活化的干扰素α前蛋白
公开(公告)号：US08399219B2
公开(公告)日：2013-03-19
申请号：US12711199
申请日：2010-02-23
申请人： Nancy E. Stagliano , James W. West , Kathryn Kamath , Paul H. Bessette , Jason Sagert
发明人： Nancy E. Stagliano , James W. West , Kathryn Kamath , Paul H. Bessette , Jason Sagert
IPC分类号： C12P21/04 , C12N5/10 , C12N15/00 , A61K38/21 , C07H21/04
CPC分类号： C07K14/56 , A61K38/00 , A61K47/64 , A61K47/65 , C07K14/00 , C07K14/555 , C07K14/565 , C07K14/57 , C07K14/705 , C07K16/00 , C07K19/00 , C07K2319/10 , C07K2319/31 , C07K2319/33 , C07K2319/50 , C07K2319/70 , C07K2319/90 , C12N15/1037 , G01N33/6866
摘要： The present disclosure provides for proprotein and activatable proprotein compositions. A proprotein contains a functional protein (i.e. a full length protein or functional fragment thereof) which is coupled to a peptide mask that inhibits the binding of the functional protein to its target or binding partner. An activatable proprotein contains a functional protein coupled to a peptide mask, and further coupled to an activatable linker, wherein in an non-activated state, the peptide mask inhibits binding of the functional protein to its target or binding partner and in an activated state the peptide mask does not inhibit binding of the functional protein to its target or binding partner. Proproteins can provide for reduced toxicity and adverse side effects that could otherwise result from binding of a functional protein at non-treatment sites if it were not inhibited from binding its binding partner. Proproteins can further provide improved biodistribution characteristics. Proproteins containing a peptide mask can display a longer in vivo or serum half-life than the corresponding functional protein not containing a peptide mask. The disclosure further provides methods of screening for, making, and using these proproteins.
摘要翻译：本公开内容提供了蛋白质和可激活的前蛋白组合物。前蛋白含有功能蛋白（即其全长蛋白质或其功能片段），其与抑制功能蛋白与其靶标或结合配偶体的结合的肽掩模偶联。可激活的蛋白质包含与肽掩模偶联的功能性蛋白质，并进一步与可活化接头偶联，其中在非活化状态下，肽掩模抑制功能性蛋白质与其靶标或结合配偶体的结合，并且在活化状态下肽掩模不抑制功能蛋白与其靶或结合配偶体的结合。前体蛋白可以提供如果不抑制结合其结合配偶体的功能性蛋白质在非处理部位的结合，则可以提供降低的毒性和不良副作用。前体蛋白可进一步提供改善的生物分布特征。含有肽掩模的前体蛋白可以显示比不含肽掩模的相应功能蛋白质更长的体内或血清半衰期。本公开进一步提供筛选，制备和使用这些蛋白质的方法。

2. 发明授权

US08513390B2 Modified antibody compositions, methods of making and using thereof 有权
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.

3. 发明申请

US20120207756A1 Modified Antibody Compositions, Methods of Making and Using Thereof 有权
标题翻译：改良抗体组合物，制备和使用方法
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。

4. 发明申请

US20100221212A1 PROPROTEINS AND METHODS OF USE THEREOF 有权
标题翻译：优点及其使用方法
公开(公告)号：US20100221212A1
公开(公告)日：2010-09-02
申请号：US12711199
申请日：2010-02-23
申请人： Nancy E. Stagliano , James W. West , Kathryn Kamath , Paul H. Bessette , Jason Sagert
发明人： Nancy E. Stagliano , James W. West , Kathryn Kamath , Paul H. Bessette , Jason Sagert
IPC分类号： A61K38/21 , C07K14/00 , C07K14/555 , C07K16/00 , A61K38/16 , A61K39/395 , A61P35/04
CPC分类号： C07K14/56 , A61K38/00 , A61K47/64 , A61K47/65 , C07K14/00 , C07K14/555 , C07K14/565 , C07K14/57 , C07K14/705 , C07K16/00 , C07K19/00 , C07K2319/10 , C07K2319/31 , C07K2319/33 , C07K2319/50 , C07K2319/70 , C07K2319/90 , C12N15/1037 , G01N33/6866
摘要： The present disclosure provides for proprotein and activatable proprotein compositions. A proprotein contains a functional protein (i.e. a full length protein or functional fragment thereof) which is coupled to a peptide mask that inhibits the binding of the functional protein to its target or binding partner. An activatable proprotein contains a functional protein coupled to a peptide mask, and further coupled to an activatable linker, wherein in an non-activated state, the peptide mask inhibits binding of the functional protein to its target or binding partner and in an activated state the peptide mask does not inhibit binding of the functional protein to its target or binding partner. Proproteins can provide for reduced toxicity and adverse side effects that could otherwise result from binding of a functional protein at non-treatment sites if it were not inhibited from binding its binding partner. Proproteins can further provide improved biodistribution characteristics. Proproteins containing a peptide mask can display a longer in vivo or serum half-life than the corresponding functional protein not containing a peptide mask. The disclosure further provides methods of screening for, making, and using these proproteins.
摘要翻译：本公开内容提供了蛋白质和可激活的前蛋白组合物。前蛋白含有功能蛋白（即其全长蛋白质或其功能片段），其与抑制功能蛋白与其靶标或结合配偶体的结合的肽掩模偶联。可激活的蛋白质包含与肽掩模偶联的功能性蛋白质，并进一步与可活化接头偶联，其中在非活化状态下，肽掩模抑制功能性蛋白质与其靶标或结合配偶体的结合，并且在活化状态下肽掩模不抑制功能蛋白与其靶或结合配偶体的结合。前体蛋白可以提供如果不抑制结合其结合配偶体的功能性蛋白质在非处理部位的结合，则可以提供降低的毒性和不良副作用。前体蛋白可进一步提供改善的生物分布特征。含有肽掩模的前体蛋白可以显示比不含肽掩模的相应功能蛋白质更长的体内或血清半衰期。本公开进一步提供筛选，制备和使用这些蛋白质的方法。

5. 发明申请

US20100189651A1 MODIFIED ANTIBODY COMPOSITIONS, METHODS OF MAKING AND USING THEREOF 审中-公开
标题翻译：改性抗体组合物，制备方法及其用途
公开(公告)号：US20100189651A1
公开(公告)日：2010-07-29
申请号：US12686344
申请日：2010-01-12
申请人： Nancy E. Stagliano , James W. West , Kathryn Kamath , Paul H. Bessette , Frederick Gluck , Jason Sagert , Patrick Daugherty
发明人： Nancy E. Stagliano , James W. West , Kathryn Kamath , Paul H. Bessette , Frederick Gluck , Jason Sagert , Patrick Daugherty
IPC分类号： A61K49/00 , C07K1/107 , C07K16/00 , A61K39/395 , A61P35/00
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，还原或光解去除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。

6. 发明授权

US08563269B2 Modified antibody compositions, methods of making and using thereof 有权
标题翻译：改良的抗体组合物，其制备和使用方法
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。

7. 发明授权

US08529898B2 Activatable binding polypeptides and methods of identification and use thereof 有权
公开(公告)号：US08529898B2
公开(公告)日：2013-09-10
申请号：US13413447
申请日：2012-03-06
申请人： Patrick Sean Daugherty , Nancy Stagliano , Jerry Thomas , Kathryn Kamath , James W. West , Sanjay Khare , Jason Sagert
发明人： Patrick Sean Daugherty , Nancy Stagliano , Jerry Thomas , Kathryn Kamath , James W. West , Sanjay Khare , Jason Sagert
IPC分类号： C07K16/22 , C07K16/46 , C07K14/00 , A61K39/00 , A61K49/16
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.

8. 发明授权

US08518404B2 Activatable binding polypeptides and methods of identification and use thereof 有权
标题翻译：可活化的结合多肽及其鉴定和使用的方法
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。

9. 发明申请

US20120237977A1 Activatable Binding Polypeptides and Methods of Identification and Use Thereof 有权
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.

10. 发明申请

US20120244154A1 Activatable Binding Polypeptides and Methods of Identification and Use Thereof 有权
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.

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