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US 12,624,077 B2Granted
CXCR3 ligand
AssigneeChugai Seiyaku Kabushiki Kaisha
InventorsYohei Yamamoto, Mika Sakurai, Kenta Haraya
Life of this patent
Estimating the term…
Abstract
The present disclosure relates to CXCR3 ligands having resistance to DPPIV and having CXCR3-expressing cell migration-inducing activity. The present disclosure specifically relates to N-terminal amino acid modifications and N-terminal amino acid sequences important for resistance to DPPIV and CXCR3-expressing cell migration-inducing activity.
Claims10
A C-X-C Motif Chemokine Receptor 3 (CXCR3) ligand, wherein the CXCR3 ligand comprises:
- a human C-X-C motif chemokine 10 (CXCL10) variant derived from human CXCL10 (SEQ ID NO:
- 60), wherein the N-terminal sequence of the CXCL10 variant is selected from the group consisting of:
- (a1) V-X1-L, wherein X1 is F, G, I, K, L, M, T, V, W, or Y and wherein V-X1-L is substituted for the N-terminal V-P-L amino acid residues of human CXCL10;
- (a2) X2-V-P, wherein X2 is A, F, G, H, I, K, L, N, P, Q, R, S, T, V, W, or Y and wherein X2 is an amino acid residue added at the N-terminus of the N-terminal V-P amino acid residues of human CXCL10;
- (a3) V-X3-P, wherein X3 is A, F, G, H, I, K, L, M, Q, R, S, T, V, W, or Y and wherein X3 is an amino acid residue inserted between the N-terminal V-P amino acid residues of human CXCL10;
- and,
- (a4) P-L-S wherein the valine residue at the N-terminus of human CXCL10 is deleted;
- or, a human C-X-C motif chemokine 11 (CXCL11) variant derived from human CXCL11 (SEQ ID NO:
- 61) or a human CXCL10-human CXCL11 chimeric protein (ITIP) variant derived from ITIP (SEQ ID NO:
- 63), wherein the N-terminal sequence of the CXCL11 variant or the chimeric protein ITIP variant is selected from the group consisting of:
- (a5) X4-F-P, wherein X4 is A, D, E, F, G, H, I, K, L, M, N, P, Q, S, T, V, W, or Y and wherein X4 is an amino acid residue added at the N-terminus of the N-terminal F-P amino acid residues of human CXCL11 or the chimeric protein ITIP;
- (a6) F-X5-M, wherein X5 is A, D, E, G, H, I, M, N, Q, R, S, T, V, W, or Y and wherein X5 is an amino acid residue substitution of proline (P) at the N-terminal F-P-M amino acid residues of human CXCL11 or the chimeric protein ITIP variant;
- and,
- (a7) F-X6-P, wherein X6 is A, D, E, F, G, H, L, M, N, P, Q, S, T, W, or Y and wherein X6 is an amino acid residue inserted between the N-terminal F-P amino acid residues of human CXCL11 or the chimeric protein ITIP variant.
11 more elements
A C-X-C Motif Chemokine Receptor 3 (CXCR3) ligand, wherein the CXCR3 ligand comprises
- a human C-X-C motif chemokine 10 (CXCL10) variant derived from human CXCL10 (SEQ ID NO:
- 60) a comprising substitution of the V-P-L-S-R-T-V-R sequence at the N-terminus of human CXCL10 with a sequence selected from the group consisting of:
- (b1) V-X1-L-S-R-T-V-R, wherein X1 is F, G, I, K, L, M, T, V, W, or Y (SEQ ID NO:
- 205);
- (b2) X2-V-P-L-S-R-T-V-R, wherein X2 is A, F, G, H, I, K, L, N, P, Q, R, S, T, V, W, or Y (SEQ ID NO:
- 206);
- (b3) V-X3-P-L-S-R-T-V-R, wherein X3 is A, F, G, H, I, K, L, M, Q, R, S, T, V, W, or Y (SEQ ID NO:
- 207);
- and,
- (b4) P-L-S-R-T-V-R (SEQ ID NO:
- 208), or
- a human C-X-C motif chemokine 11 (CXCL1l) variant derived from human CXCL11 (SEQ ID NO:
- 61) or a human CXCL10-human CXCL11 chimeric protein (ITIP) variant a derived from ITIP (SEQ ID NO:
- 63), wherein the F-P-M-F-K-R-G-R sequence at the N-terminus of the human CXCL11 or human CXCL10-human CXCL11 chimeric protein (ITIP) is substituted with a sequence selected from the group consisting of:
- (b5) X4-F-P-M-F-K-R-G-R, wherein X4 is A, D, E, F, G, H, I, K, L, M, N, P, Q, S, T, V, W, or Y (SEQ ID NO:
- 209);
- (b6) F-X5-M-F-K-R-G-R, wherein X5 is A, D, E, G, H, I, M, N, Q, R, S, T, V, W, or Y (SEQ ID NO:
- 210);
- and
- (b7) F-X6-P-M-F-K-R-G-R, wherein X6 is A, D, E, F, G, H, L, M, N, P, Q, S, T, W, or Y (SEQ ID NO:
- 211).
18 more elements
Dependencies are inferred from the claim text.