Abstract: The invention relates in one aspect to compounds, pharmaceutical compositions thereof, and methods using the same for selectively activating either all or a single isoform of Akt. Isoform selective-targeting is necessary for avoiding pathologies driven by concomitantly activated Akt1, Akt2 and/or Akt3.

Abstract: Provided herein are recombinant CTLA-4 binding proteins, which are, inter alia, useful for the treatment of cancer. The recombinant proteins provided herein are, inter alia, capable of binding CTLA-4 proteins on a tumor cell. In a first aspect, there is provided a recombinant CTLA-4 binding protein including (i) a CTLA-4 binding domain; (ii) a CTLA-4 binding domain masking peptide; and (iii) a cleavable peptide linker connecting the CTLA-4 binding domain masking peptide to the CTLA-4 binding domain. In another aspect, there is provided a dimerizing domain covalently attached to the CTLA-4 binding domain, wherein the binding protein domains are bound together.

Abstract: In one embodiment, a masked monoclonal antibody (mAb) is provided, the mAb, encoded by a nucleic acid sequence or an amino acid sequence molecule comprising a signal sequence, a masking epitope sequence, a linker sequence that is cleavable by a protease specific to a target tissue; and an antibody or a functional fragment thereof. In another embodiment, a masked monoclonal antibody (mAb) is provided, which includes a therapeutic mAb and a mask, the mask comprising protein A and protein L attached by a protease cleavable linker.

Abstract: In one embodiment, a masked monoclonal antibody (mAb) is provided, the mAb, encoded by a nucleic acid sequence or an amino acid sequence molecule comprising a signal sequence, a masking epitope sequence, a linker sequence that is cleavable by a protease specific to a target tissue; and an antibody or a functional fragment thereof. In another embodiment, a masked monoclonal antibody (mAb) is provided, which includes a therapeutic mAb and a mask, the mask comprising protein A and protein L attached by a protease cleavable linker.

Abstract: Provided herein are recombinant masking proteins and recombinant ligand proteins useful in treating cancer, neurodegenerative disease, and cardiovascular disease. The recombinant masking proteins provided herein may, inter alia, be used as non-covalent masks of antagonists of, for example, cellular growth factors (e.g., TNF) or cell surface proteins (e.g., CTLA-4).

Abstract: In one embodiment, a masked monoclonal antibody (mAb) is provided, the mAb, encoded by a nucleic acid sequence or an amino acid sequence molecule comprising a signal sequence, a masking epitope sequence, a linker sequence that is cleavable by a protease specific to a target tissue; and an antibody or a functional fragment thereof. In another embodiment, a cross-masked mAb heterodimer complex is provided, comprising a first masked mAb, comprising a first signal sequence, a first masking epitope sequence, a first linker that is cleavable by a protease specific to a target tissue, and a first antibody or fragment thereof; and a second masked mAb, comprising a second signal sequence, a second masking epitope sequence, a second linker that is cleavable by a protease specific to a target tissue, and a second antibody or fragment thereof.

Abstract: Provided herein are recombinant CTLA-4 binding proteins, which are, inter alia, useful for the treatment of cancer. The recombinant proteins provided herein are, inter alia, capable of binding CTLA-4 proteins on a tumor cell. In a first aspect, there is provided a recombinant CTLA-4 binding protein including (i) a CTLA-4 binding domain; (ii) a CTLA-4 binding domain masking peptide; and (iii) a cleavable peptide linker connecting the CTLA-4 binding domain masking peptide to the CTLA-4 binding domain. In another aspect, there is provided a dimerizing domain covalently attached to the CTLA-4 binding domain, wherein the binding protein domains are bound together.

Abstract: Provided herein are recombinant masking proteins and recombinant ligand proteins useful in treating cancer, neuro-degenerative disease, and cardiovascular disease. The recombinant masking proteins provided herein may, inter alia, be used as non-covalent masks of antagonists of, for example, cellular growth factors (e.g., TNF) or cell surface proteins (e.g., CTLA-4).

Abstract: Provided herein are recombinant CTLA-4 binding proteins, which are, inter alia, useful for the treatment of cancer. The recombinant proteins provided herein are, inter alia, capable of binding CTLA-4 proteins on a tumor cell. In a first aspect, there is provided a recombinant CTLA-4 binding protein including (i) a CTLA-4 binding domain; (ii) a CTLA-4 binding domain masking peptide; and (iii) a cleavable peptide linker connecting the CTLA-4 binding domain masking peptide to the CTLA-4 binding domain. In another aspect, there is provided a dimerizing domain covalently attached to the CTLA-4 binding domain, wherein the binding protein domains are bound together.

Abstract: In one embodiment, a masked monoclonal antibody (mAb) is provided, the mAb, encoded by a nucleic acid sequence or an amino acid sequence molecule comprising a signal sequence, a masking epitope sequence, a linker sequence that is cleavable by a protease specific to a target tissue; and an antibody or a functional fragment thereof. In another embodiment, a masked monoclonal antibody (mAb) is provided, which includes a therapeutic mAb and a mask, the mask comprising protein A and protein L attached by a protease cleavable linker.

Abstract: Provided herein are recombinant masking proteins and recombinant ligand proteins useful in treating cancer, neurodegenerative disease, and cardiovascular disease. The recombinant masking proteins provided herein may, inter alia, be used as non-covalent masks of antagonists of, for example, cellular growth factors (e.g., TNF) or cell surface proteins (e.g., CTLA-4).

Abstract: In one embodiment, a masked monoclonal antibody (mAb) is provided, the mAb, encoded by a nucleic acid sequence or an amino acid sequence molecule comprising a signal sequence, a masking epitope sequence, a linker sequence that is cleavable by a protease specific to a target tissue; and an antibody or a functional fragment thereof. In another embodiment, a masked monoclonal antibody (mAb) is provided, which includes a therapeutic mAb and a mask, the mask comprising protein A and protein L attached by a protease cleavable linker.

Abstract: Provided herein are recombinant CTLA-4 binding proteins, which are, inter alia, useful for the treatment of cancer. The recombinant proteins provided herein are, inter alia, capable of binding CTLA-4 proteins on a tumor cell. In a first aspect, there is provided a recombinant CTLA-4 binding protein including (i) a CTLA-4 binding domain; (ii) a CTLA-4 binding domain masking peptide; and (iii) a cleavable peptide linker connecting the CTLA-4 binding domain masking peptide to the CTLA-4 binding domain. In another aspect, there is provided a dimerizing domain covalently attached to the CTLA-4 binding domain, wherein the binding protein domains are bound together.

Abstract: Provided herein are recombinant masking proteins and recombinant ligand proteins useful in treating cancer, neurodegenerative disease, and cardiovascular disease. The recombinant masking proteins provided herein may, inter alia, be used as non-covalent masks of antagonists of, for example, cellular growth factors (e.g., TNF) or cell surface proteins (e.g., CTLA-4).

Abstract: In one embodiment, a masked monoclonal antibody (mAb) is provided, the mAb, encoded by a nucleic acid sequence or an amino acid sequence molecule comprising a signal sequence, a masking epitope sequence, a linker sequence that is cleavable by a protease specific to a target tissue; and an antibody or a functional fragment thereof. In another embodiment, a cross-masked mAb heterodimer complex is provided, comprising a first masked mAb, comprising a first signal sequence, a first masking epitope sequence, a first linker that is cleavable by a protease specific to a target tissue, and a first antibody or fragment thereof; and a second masked mAb, comprising a second signal sequence, a second masking epitope sequence, a second linker that is cleavable by a protease specific to a target tissue, and a second antibody or fragment thereof.

Abstract: In one embodiment, a masked monoclonal antibody (mAb) is provided, the mAb, encoded by a nucleic acid sequence or an amino acid sequence molecule comprising a signal sequence, a masking epitope sequence, a linker sequence that is cleavable by a protease specific to a target tissue; and an antibody or a functional fragment thereof. In another embodiment, a cross-masked mAb heterodimer complex is provided, comprising a first masked mAb, comprising a first signal sequence, a first masking epitope sequence, a first linker that is cleavable by a protease specific to a target tissue, and a first antibody or fragment thereof; and a second masked mAb, comprising a second signal sequence, a second masking epitope sequence, a second linker that is cleavable by a protease specific to a target tissue, and a second antibody or fragment thereof.

Abstract: In one embodiment, a masked monoclonal antibody (mAb) is provided, the mAb, encoded by a nucleic acid sequence or an amino acid sequence molecule comprising a signal sequence, a masking epitope sequence, a linker sequence that is cleavable by a protease specific to a target tissue; and an antibody or a functional fragment thereof. In another embodiment, a cross-masked mAb heterodimer complex is provided, comprising a first masked mAb, comprising a first signal sequence, a first masking epitope sequence, a first linker that is cleavable by a protease specific to a target tissue, and a first antibody or fragment thereof; and a second masked mAb, comprising a second signal sequence, a second masking epitope sequence, a second linker that is cleavable by a protease specific to a target tissue, and a second antibody or fragment thereof.

Abstract: In one embodiment, a masked monoclonal antibody (mAb) is provided, the mAb, encoded by a nucleic acid sequence or an amino acid sequence molecule comprising a signal sequence, a masking epitope sequence, a linker sequence that is cleavable by a protease specific to a target tissue; and an antibody or a functional fragment thereof. In another embodiment, a cross-masked mAb heterodimer complex is provided, comprising a first masked mAb, comprising a first signal sequence, a first masking epitope sequence, a first linker that is cleavable by a protease specific to a target tissue, and a first antibody or fragment thereof; and a second masked mAb, comprising a second signal sequence, a second masking epitope sequence, a second linker that is cleavable by a protease specific to a target tissue, and a second antibody or fragment thereof.

Abstract: In one embodiment, a masked monoclonal antibody (mAb) is provided, the mAb, encoded by a nucleic acid sequence or an amino acid sequence molecule comprising a signal sequence, a masking epitope sequence, a linker sequence that is cleavable by a protease specific to a target tissue; and an antibody or a functional fragment thereof. In another embodiment, a cross-masked mAb heterodimer complex is provided, comprising a first masked mAb, comprising a first signal sequence, a first masking epitope sequence, a first linker that is cleavable by a protease specific to a target tissue, and a first antibody or fragment thereof; and a second masked mAb, comprising a second signal sequence, a second masking epitope sequence, a second linker that is cleavable by a protease specific to a target tissue, and a second antibody or fragment thereof.

Abstract: Masking ligands for reversibly concealing the antigen-binding site of an antibody comprise epitopes of the antibody and a cleavable linker. Methods for making masking ligands comprise joining at least two copies of the epitope of an antibody to a cleavable polypeptide linker.