Cleavable linkers
AssigneeXilio Development, Inc.
InventorsDheeraj Singh Tomar, Magali Pederzoli-Ribeil, Giselle Marcelline Knudsen
Life of this patent
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Abstract
The present invention discloses proteolytically cleavable peptide (CP) substrates, polypeptides, polypeptide constructs and prodrug constructs comprising the proteolytically cleavable peptides (e.g., cytokine prodrugs), and methods of use of the same.
Claims29
A polypeptide comprising a proteolytically cleavable peptide linker, wherein the linker comprises a proteolytically cleavable peptide (CP) consisting of the amino acid sequence PVSLRSGS (SEQ ID NO:1) or GMPKDLYHAS (SEQ ID NO:2), or RPLALWRS (SEQ ID NO:3), or TQKPLGLS (SEQ ID NO:4), or APAGLIVPYN (SEQ ID NO:5), or PANLVAPDP (SEQ ID NO:6), or IVGRPRHQGV (SEQ ID NO:7), or RSKYLATA (SEQ ID NO:8).
A polypeptide construct comprising a proteolytically cleavable peptide linker, wherein the linker comprises a proteolytically cleavable peptide (CP) consisting of the amino acid sequence PVSLRSGS (SEQ ID NO:1) or GMPKDLYHAS (SEQ ID NO:2), or RPLALWRS (SEQ ID NO:3), or TQKPLGLS (SEQ ID NO:4), or APAGLIVPYN (SEQ ID NO:5), or PANLVAPDP (SEQ ID NO:6), or IVGRPRHQGV (SEQ ID NO:7), or RSKYLATA (SEQ ID NO:8).
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A targeted cytokine comprising:
- a) a targeting moiety;
- b) a cytokine or a fragment thereof;
- c) a masking moiety;
- and
- d) an Fc domain comprising a first Fc polypeptide linked to the cytokine or a fragment thereof through a first linker and a second Fc polypeptide linked to the masking moiety through a second linker, wherein the first or the second linker is a cleavable linker such that the masking moiety releases the cytokine or a fragment thereof upon cleavage;
- wherein the targeting moiety is linked to the Fc domain through one or both of the first and second Fc polypeptides;
- and
- wherein at least the first linker or the second linker is a proteolytically cleavable peptide linker comprising a proteolytically cleavable peptide (CP) consisting of the amino acid sequence PVSLRSGS (SEQ ID NO:1), or GMPKDLYHAS (SEQ ID NO:2), or RPLALWRS (SEQ ID NO:3), or TQKPLGLS (SEQ ID NO:4), or APAGLIVPYN (SEQ ID NO:5), or PANLVAPDP (SEQ ID NO:6), or IVGRPRHQGV (SEQ ID NO:7), or RSKYLATA (SEQ ID NO:8).
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Dependencies are inferred from the claim text.