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Publication Number
US-12384845-B2
Publication Date
2025-08-12
Expiration Date
Abstract
The invention provides activatable masked anti-CTLA4 binding proteins (e.g., antibodies, bispecific antibodies, and chimeric receptors) and their use in treating and preventing cancer, as well as compositions and kits comprising the activatable masked anti-CTLA4 binding proteins.
Core Innovation
The invention relates to activatable masked CTLA4 binding proteins, including masked antibodies, masked bispecific antibodies, and masked chimeric receptors, that are systemically inert until activation by protease cleavage. The CTLA4-binding moiety is provided in a masked form such that a masking peptide occludes binding activity and is removed upon cleavage by a cleavable peptide linker.
A masked antibody format is described in which an anti-CTLA4 antibody or antigen-binding fragment includes a light chain variable (VL) domain and a heavy chain variable (VH) domain. The antibody comprises a masking peptide having the amino acid sequence of SEQ ID NO: 5 linked via a linker comprising a cleavable peptide to an amino-terminus of the VL domain, and the cleavable peptide comprises the amino acid sequence of SEQ ID NO: 86, with additional optional spacer linker sequences.
The disclosed content provides examples of masking, cleavable, and spacer peptide sequences, specifies antibody structure elements via particular CDR-L and CDR-H sequences and variants, and includes biological production and therapeutic composition aspects. The activatable masking concept is also presented in conjugate formats such as masked antibody-drug conjugates and radioconjugates, and in neoplastic disease treatment.
Claims Coverage
The independent claims define a masked anti-CTLA4 antibody architecture with an activatable masking peptide linked through a cleavable peptide linker to the VL domain, together with specific CDR-L and CDR-H sequence options. Across the inputs, there are 3 main inventive features.
Masked anti-ctla4 antibody with peptide masking linked to vl amino-terminus
An anti-CTLA4 antibody or antigen-binding fragment with a masking peptide comprising the amino acid sequence of SEQ ID NO: 5 linked via a linker comprising a cleavable peptide to an amino-terminus of the VL domain.
Cleavable peptide linker having seq id no: 86
The linker comprising a cleavable peptide comprises a cleavable peptide comprising the amino acid sequence of SEQ ID NO: 86.
Defined vl and vh cdr sequence sets for anti-ctla4 binding
The VL domain comprises CDR-L1, CDR-L2, and CDR-L3 sequences and the VH domain comprises CDR-H1, CDR-H2, and CDR-H3 sequences, with either the SEQ ID NOs 408-410 and 411-413 set or the SEQ ID NOs 438-440 and 441-443 set.
Overall, the claim coverage centers on a masked anti-CTLA4 antibody in which masking peptide SEQ ID NO: 5 is attached through a cleavable peptide linker including SEQ ID NO: 86 to the amino-terminus of the VL domain, together with defined CDR-L and CDR-H sequence sets.
Stated Advantages
Systemically inert until activation by protease cleavage.
Documented Applications
Treating or preventing neoplastic cancers in subjects.
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