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US 2010/0135997 A1Published application
Polypeptide monomers and dimers containing mutated ilt
AssigneeMedgene, Limited
InventorsBent Karsten Jakobsen, Yi Li, Ruth Karen Moysey
Life of this patent
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Abstract
The present invention provides monomeric and dimeric polypeptide fusions comprising mutated human ILT molecules and immunoglobulin Fc segments. Such compostions are useful, either alone or associated with a therapeutic agent, for targeting cells expressing Class I pMHC molecules.
Claims36
A polypeptide comprising an ILT-like segment and an Fc-like segment wherein either
- (a) the ILT-like segment is the N-terminal segment of the polypeptide and has at least a 45% identity and/or 55% similarity to SEQ ID NO:
- 19;
- and said N-terminal segment per se has the property of (i) binding to a given Class I pMHC with a KD of less than or equal to 1 μM and/or with an off-rate (koff) of 2 S−1 or slower, and (ii) inhibiting CD8 binding to the given pMHC to a greater extent than the polypeptide SEQ ID NO:
- 3;
- and the Fc-like segment is the C-terminal segment of the polypeptide and comprises a portion of the constant domain of one of the heavy chains of an immunoglobulin having at least 70% identity and/or 80% similarity to the corresponding portion of SEQ ID NO 139;
- or
- (b) the Fc-like segment is the N-terminal segment of the polypeptide and comprises a portion of the constant domain of one of the heavy chains of an immunoglobulin having at least 70% identity and/or 80% similarity to the corresponding portion of SEQ ID 139;
- and the ILT-like segment is the C-terminal segment of the polypeptide and has at least a 45% identity and/or 55% similarity to SEQ ID NO:
- 19;
- and said C-terminal segment per se has the property of (i) binding to a given Class I pMHC with a KD of less than or equal to 1 μM and/or with an off-rate (koff) of 2 S−1 or slower, and (ii) inhibiting CD8 binding to the given pMHC to a greater extent than the polypeptide SEQ ID NO:
- 3,
- wherein the polypeptide is arranged as a monomeric polypeptide or as a polypeptide dimer comprising a first polypeptide and a second polypeptide, in which dimer
- (i) the first and/or the second polypeptide comprises an ILT-like segment having at least a 45% identity and/or 55% similarity to SEQ ID NO:
- 19;
- (ii) said ILT-like segment(s) per se have the property of (a) binding to a given Class I pMHC with a KD of less than or equal to 1 μM and/or with an off-rate (kOff) of 2 S−1 or slower, and (b) inhibiting CD8 binding to the given pMHC to a greater extent than the polypeptide SEQ ID NO:
- 3;
- (iii) each of the first and second polypeptides comprises an Fc-like segment comprising a portion of the constant domain of one of the heavy chains of an immunoglobulin having at least 70% identity and/or 80% similarity to the corresponding portion of SEQ ID NO:
- 139;
- and wherein either (a) the ILT-like segment(s) is/are the N-terminal segment(s) of the first and/or second polypeptides, and the Fc-like segments are the C-terminal segments of the first and second polypeptides or (b) the Fc-like segments are the N-terminal segments of the first and/or second polypeptides, and the ILT-like segment(s) is/are the C-terminal segment(s) of the first and second polypeptides.
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Dependencies are inferred from the claim text.