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1. 发明申请

WO2010096838A3 PROPROTEINS AND METHODS OF USE THEREOF 审中-公开
标题翻译：优点及其使用方法
公开(公告)号：WO2010096838A3
公开(公告)日：2014-04-03
申请号：PCT/US2010025121
申请日：2010-02-23
申请人： CYTOMX THERAPEUTICS INC , STAGLIANO NANCY E , WEST JAMES W , KAMATH KATHRYN , BESSETTE PAUL H , SAGERT JASON
发明人： STAGLIANO NANCY E , WEST JAMES W , KAMATH KATHRYN , BESSETTE PAUL H , SAGERT JASON
IPC分类号： A01N37/18 , A61K38/10
CPC分类号： C07K14/56 , A61K38/00 , A61K47/48246 , A61K47/48338 , 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. 发明申请

WO2010081173A3 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：WO2010081173A3
公开(公告)日：2010-11-04
申请号：PCT/US2010020820
申请日：2010-01-12
申请人： CYTOMX THERAPEUTICS LLC , STAGLIANO NANCY E , WEST JAMES W , KAMATH KATHRYN , BESSETTE PAUL H , GLUCK FRED , SAGERT JASON , DAUGHERTY PATRICK
发明人： STAGLIANO NANCY E , WEST JAMES W , KAMATH KATHRYN , BESSETTE PAUL H , GLUCK FRED , SAGERT JASON , DAUGHERTY PATRICK
IPC分类号： C07K16/18 , A61K39/395 , A61P35/00 , C12N15/13 , G01N33/53
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 photo lysing 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，还原或照相裂解的试剂存在下，通过CM的切割，还原或光解来除去MM，使得目标物更容易接近 CM。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。

3. 发明申请

WO2009025846A3 ACTIVATABLE BINDING POLYPEPTIDES AND METHODS OF IDENTIFICATION AND USE THEREOF 审中-公开
标题翻译：活化结合多肽及其鉴定和使用方法
公开(公告)号：WO2009025846A3
公开(公告)日：2009-05-14
申请号：PCT/US2008009974
申请日：2008-08-21
申请人： UNIV CALIFORNIA , CYTOMX LLC , DAUGHERTY PATRICK SEAN , STAGLIANO NANCY E , THOMAS JERRY , KAMATH KATHRYN , WEST JAMES W , KHARE SANJAY
发明人： DAUGHERTY PATRICK SEAN , STAGLIANO NANCY E , THOMAS JERRY , KAMATH KATHRYN , WEST JAMES W , KHARE SANJAY
IPC分类号： C07K14/00 , A61K39/395
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：本公开提供了包含靶结合部分（TBM），掩蔽部分（MM）和可切割部分（CM）的可活化结合多肽（ABP）。本公开内容提供了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“可活化”构象，使得在未切割时至少一个TBM对靶的接近性低于在能够切割CM的切割剂存在下切割CM后。本公开还提供了候选ABP的文库，筛选以鉴定这些ABP的方法，以及使用方法。本公开还提供了具有结合VEGF，CTLA-4或VCAM的TBM的ABP，具有结合VEGF的第一TBM和结合FGF的第二TBM的ABP，以及组合物和使用方法。

4. 发明专利

AU2010215761B2 Proproteins and methods of use thereof 未知
公开(公告)号：AU2010215761B2
公开(公告)日：2017-04-06
申请号：AU2010215761
申请日：2010-02-23
申请人： CYTOMX THERAPEUTICS INC
发明人： STAGLIANO NANCY E , WEST JAMES W , KAMATH KATHRYN , BESSETTE PAUL H , SAGERT JASON
IPC分类号： A01N37/18 , A61K38/10
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.

5. 发明专利

AU2008289441A1 Activatable binding polypeptides and methods of identification and use thereof 未知
公开(公告)号：AU2008289441A1
公开(公告)日：2009-02-26
申请号：AU2008289441
申请日：2008-08-21
申请人： CYTOMX THERAPEUTICS INC , UNIV CALIFORNIA
发明人： DAUGHERTY PATRICK SEAN , WEST JAMES W , KHARE SANJAY , THOMAS JERRY , KAMATH KATHRYN , STAGLIANO NANCY E
IPC分类号： C07K14/00 , A61K39/395
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 TMBs 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.

6. 发明公开

EP2398494A4 Proproteins and methods of use thereof 审中-公开
标题翻译： PROPROTEINE UND ANWENDUNGSVERFAHRENDAFÜR
公开(公告)号：EP2398494A4
公开(公告)日：2015-10-28
申请号：EP10744488
申请日：2010-02-23
申请人： CYTOMX THERAPEUTICS INC
发明人： STAGLIANO NANCY E , WEST JAMES W , KAMATH KATHRYN , BESSETTE PAUL H , SAGERT JASON
IPC分类号： A61K38/21 , A61K38/00 , A61K38/16 , A61K39/395 , A61K47/48 , A61P35/04 , C07K14/00 , C07K14/555 , C07K14/56 , C07K14/565 , C07K14/57 , C07K16/00 , C07K19/00 , G01N33/68
CPC分类号： C07K14/56 , A61K38/00 , A61K47/48246 , A61K47/48338 , 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。前列腺素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。前体蛋白可以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。

7. 发明专利

AU2020203143A1 Modified antibody compositions, methods of making and using thereof 未知
公开(公告)号：AU2020203143A1
公开(公告)日：2020-06-04
申请号：AU2020203143
申请日：2020-05-13
申请人： CYTOMX THERAPEUTICS INC
发明人： STAGLIANO NANCY E , WEST JAMES W , KAMATH KATHRYN , BESSETTE PAUL H , GLUCK FRED , SAGERT JASON GARY , DAUGHERTY PATRICK
IPC分类号： C07K16/18 , A61K39/395 , A61P35/00 , C12N15/13 , G01N33/53
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 photo lysing the CM. The disclosure further provides methods of making and using such modified antibodies and activatable antibodies.

8. 发明专利

AU2018214147B2 Modified Antibody Compositions, Methods of Making and Using Thereof 未知
公开(公告)号：AU2018214147B2
公开(公告)日：2020-06-04
申请号：AU2018214147
申请日：2018-08-10
申请人： CYTOMX THERAPEUTICS INC
发明人： STAGLIANO NANCY E , WEST JAMES W , KAMATH KATHRYN , BESSETTE PAUL H , GLUCK FRED , SAGERT JASON GARY , DAUGHERTY PATRICK
IPC分类号： C07K16/18 , A61K39/395 , A61P35/00 , C12N15/13 , G01N33/53
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 photo lysing the CM. The disclosure further provides methods of making and using such modified antibodies and activatable antibodies.

9. 发明专利

AU2017201682A1 Proproteins and Methods of Use Thereof 未知
公开(公告)号：AU2017201682A1
公开(公告)日：2017-03-30
申请号：AU2017201682
申请日：2017-03-10
申请人： CYTOMX THERAPEUTICS INC
发明人： STAGLIANO NANCY E , WEST JAMES W , KAMATH KATHRYN , BESSETTE PAUL H , SAGERT JASON GARY
IPC分类号： A01N37/18 , A61K38/10

10. 发明专利

AU2016225810A1 Modified Antibody Compositions, Methods of Making and Using Thereof 未知
公开(公告)号：AU2016225810A1
公开(公告)日：2016-09-22
申请号：AU2016225810
申请日：2016-09-06
申请人： CYTOMX THERAPEUTICS INC
发明人： STAGLIANO NANCY E , WEST JAMES W , KAMATH KATHRYN , BESSETTE PAUL H , GLUCK FRED , SAGERT JASON , DAUGHERTY PATRICK
IPC分类号： C07K16/18 , A61K39/395 , A61P35/00 , C12N15/13 , G01N33/53
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 photo lysing the CM. The disclosure further provides methods of making and using such modified antibodies and activatable antibodies.

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