Activatable binding polypeptides and methods of identification and use thereof
First Claim
1. An activatable binding polypeptide (ABP) that in an activated state binds Cytotoxic T-Lymphocyte Antigen 4 (CTLA 4), the ABP comprising, in an N- to C-terminal direction or in a C- to N-terminal direction:
- an antigen binding domain (ABD) that specifically binds to CTLA-4,a cleavable moiety (CM), anda masking moiety (MM), wherein the MM is a peptide that inhibits binding of the ABD to CTLA-4, wherein the MM comprises an amino acid sequence selected from the group consisting of MILLCAAGRTWVEACANGR (SEQ ID NO;
63), AERLCAWAGRFCGS (SEQ ID NO;
65), WADVMPGSGVLPWTS (SEQ ID NO;
67) and SDGRMGSLELCALWGRFCGS (SEQ ID NO;
69, and wherein the CM is positioned in the ABP such that in an uncleaved state the MM interferes with specific binding of the ABD to CTLA-4 and in a cleaved state the MM does not interfere with specific binding of the ABD to CTLA-4.
6 Assignments
0 Petitions
Accused Products
Abstract
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.
161 Citations
25 Claims
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1. An activatable binding polypeptide (ABP) that in an activated state binds Cytotoxic T-Lymphocyte Antigen 4 (CTLA 4), the ABP comprising, in an N- to C-terminal direction or in a C- to N-terminal direction:
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an antigen binding domain (ABD) that specifically binds to CTLA-4, a cleavable moiety (CM), and a masking moiety (MM), wherein the MM is a peptide that inhibits binding of the ABD to CTLA-4, wherein the MM comprises an amino acid sequence selected from the group consisting of MILLCAAGRTWVEACANGR (SEQ ID NO;
63), AERLCAWAGRFCGS (SEQ ID NO;
65), WADVMPGSGVLPWTS (SEQ ID NO;
67) and SDGRMGSLELCALWGRFCGS (SEQ ID NO;
69, and wherein the CM is positioned in the ABP such that in an uncleaved state the MM interferes with specific binding of the ABD to CTLA-4 and in a cleaved state the MM does not interfere with specific binding of the ABD to CTLA-4. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25)
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Specification