Ligand having agonistic activity to mutated receptor
AssigneeChugai Seiyaku Kabushiki Kaisha
InventorsMasayuki Tsuchiya, Yuichi Hirata
Life of this patent
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Abstract
The present inventors used antibody engineering techniques to prepare functional antibodies that correspond to individual mutations in causative genes of diseases, and discovered that such antibodies enable the treatment of the diseases. Specifically, the inventors succeeded in preparing ligands, particularly minibodies, which have agonistic activity to receptors that have almost completely lost responsiveness to their natural ligands because of gene mutations (for example, a thrombopoietin (TPO) receptor whose reactivity to TPO has been markedly impaired), and which can transduce signals by interacting with these mutant receptors at levels comparable to normal.
Claims32
A ligand having agonistic activity to a mutant receptor.
A method for transducing a signal to a mutant receptor by binding a ligand.
A method for treating a disease caused by a mutant receptor, by binding a ligand to the mutant receptor.
A method of screening for a ligand having agonistic activity to a mutant receptor, where the method comprises the steps of:
- (a) contacting a test substance with the mutant receptor;
- (b) detecting a signal in the mutant receptor;
- and
- (c) selecting a ligand having agonistic activity.
A method of screening for a ligand having agonistic activity to a mutant receptor, where the method comprises the steps of:
- (a) determining agonistic activity to a normal receptor;
- (b) determining agonistic activity to the mutant receptor;
- and
- (c) selecting a ligand having greater agonistic activity to the mutant receptor than the normal receptor.
A method of screening for a ligand having agonistic activity to a normal and a mutant receptor, where the method comprises the steps of:
- (a) determining agonistic activity to the normal receptor;
- (b) determining agonistic activity to the mutant receptor;
- and
- (c) selecting a ligand having agonistic activity to both the normal and the mutant receptors.
A therapeutic agent for a disease caused by a mutant receptor, where the agent comprises a ligand of the mutant receptor.
Dependencies are inferred from the claim text.