公开(公告)号：EP3492488A1

公开(公告)日：2019-06-05

申请号：EP18200815.1

申请日：2008-08-21

申请人： The Regents of the University of California ,  CytomX Therapeutics, Inc.

发明人： DAUGHERTY, Patrick Sean ,  STAGLIANO, Nancy E. ,  THOMAS, Jerry ,  KAMATH, Kathryn ,  WEST, James W. ,  KHARE, Sanjay ,  SAGERT, Jason

IPC分类号： C07K14/00 ,  A61K39/395 ,  C07K16/22 ,  C07K16/24 ,  C07K16/28 ,  C07K16/42 ,  C12N15/10

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.

公开(公告)号：EP2385955B1

公开(公告)日：2020-08-12

申请号：EP10729683.2

申请日：2010-01-12

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： A61P1/16 ,  A61P11/00 ,  A61P13/00 ,  A61P13/08 ,  A61P15/00 ,  A61K39/00 ,  A61K47/68 ,  C07K16/00 ,  C07K16/28 ,  C07K16/22 ,  G01N33/68 ,  A61P1/18

公开(公告)号：EP2398494A2

公开(公告)日：2011-12-28

申请号：EP10744488.7

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 ,  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.