Chemokine N-terminal deletion mutations
AssigneeDana-Farber Cancer Institute, Inc.
InventorsBarrett Rollins, Yujun Zhang
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Abstract
The invention relates to mutant chemokines and pharmaceutical compositions thereof, wherein the mutant inhibits the corresponding endogenous chemokine from binding or activating a responsive receptor. The claimed mutant chemokines can be administered to a patient for the treatment or prophylaxis of a chemokine-mediated disease. The invention further relates to isolated DNAs encoding the mutant chemokines, vectors and recombinant host cells containing the same.
Claims24
A modified nucleic acid molecule which encodes a monocyte Chemoattractant Protein-1 (MCP-1) derivative capable of inhibiting the monocyte chemoattractant activity of endogenous MCP-1, with the proviso that the derivative has not been modified by the substitution of 28-tyrosine by leucine and/or the substitution of 30-arginine by valine.
A modified nucleic acid molecule which encodes a monocyte Chemoattractant Protein-1 (MCP-1) derivative capable of inhibiting monocyte chemoattractant activity of endogenous MCP-1 wherein one or more of 24-arginine, 3-aspartate and the 2-8 amino acid sequence have been deleted or substituted by one or more amino acids.
A modified nucleic acid molecule which encodes a monocyte Chemoattractant Protein-1 (MCP-1) derivative capable of inhibiting monocyte chemoattractant activity of endogenous MCP-1 wherein the MCP-1 has been modified in one or more of the following ways:
- (a) the 28-tyrosine is substituted by aspartate;
- (b) the 24-arginine is substituted by phenylalanine;
- (c) the 3-aspartate is substituted by alanine;
- and/or
- (d) the 2-8 amino acid sequence is deleted.
Dependencies are inferred from the claim text.