Methods of identifying agents which bind GPR-9-6
AssigneeMillennium Pharmaceuticals, Inc.
InventorsDavid P. Andrew, Brian A. Zabel, Paul D. Ponath
Life of this patent
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Abstract
The invention relates to an antibody or antigen-binding fragment thereof which binds to the CC chemokine receptor GPR-9-6 and blocks the binding of a ligand (e.g., TECK) to the receptor. The invention also relates to a method of identifying agents (molecules, compounds) which can bind to GPR-9-6 and inhibit the binding of a ligand (e.g., TECK) and/or modulate a function of GPR-9-6. The invention further relates to a method of modulating a function of GPR-9-6, and to the use of the antibodies, antigen-binding fragments and agents identified by the method of the invention in research, therapeutic, prophylactic and diagnostic methods.
Claims49
An antibody or antigen-binding fragment thereof, which binds to a mammalian GPR-9-6 and inhibits the binding of a ligand to said GPR-9-6.
An antibody produced by murine hybridoma 3C3 or an antigen-binding fragment thereof.
An isolated cell which produces an antibody or antigen-binding fragment thereof which binds to a mammalian GPR-9-6 and inhibits the binding of a ligand to said GPR-9-6.
The murine hybridoma 3C3.
A method of detecting a mammalian GPR-9-6 or portion thereof by in a biological sample, comprising:
- a) contacting a biological sample with an antibody or antigen-binding fragment thereof which binds to a mammalian GPR-9-6 or portion of said receptor and inhibits binding of a ligand to the receptor, under conditions appropriate for binding of said antibody or antigen-binding fragment thereof to a mammalian GPR-9-6 or portion thereof;
- and
- b) detecting binding of said antibody or antigen-binding fragment thereof;
- wherein the binding of said antibody or antigen-binding fragment thereof indicates the presence of said receptor or portion of said receptor.
A method of detecting and identifying an agent which binds to a mammalian GPR-9-6 or a ligand binding variant thereof comprising combining:
- a) a reference agent,
- b) a test agent, and
- c) a composition comprising a functional mammalian GPR-9-6 or a ligand binding variant thereof under conditions suitable for binding of said reference agent to said GPR-9-6 or ligand-binding variant thereof;
- and detecting or measuring the formation of a complex between said
- reference agent and said GPR-9-6 or a ligand binding variant thereof, wherein, a decrease in the formation of said complex relative to a suitable control indicates that said test agent binds to said GPR-9-6 or to a ligand-binding variant thereof.
The method of claim 23 wherein said cell is selected from the group consisting of MOLT-4 and MOLT-13.
A method of detecting or identifying an inhibitor of a mammalian GPR-9-6 receptor comprising:
- a) combining an agent to be tested, a ligand or promoter of said GPR-9-6 and a cell expressing said GPR-9-6 under conditions suitable for detecting a ligand- or promoter-induced response;
- and
- b) determining the ability of the test compound to inhibit said response, wherein inhibition of a ligand- or promoter-induced response by the agent is indicative that the agent is an inhibitor.
A method of treating a subject having an inflammatory disease, comprising administering an effective amount of an antagonist of a mammalian GPR-9-6 function to said subject.
A method of inhibiting GPR-9-6-mediated homing of leukocytes in a subject, comprising administering an effective amount of an antagonist of GPR-9-6 function to said subject.
A method of inhibiting GPR-9-6-mediated homing of leukocytes to mucosal tissue in a subject, comprising administering an effective amount of an antagonist of GPR-9-6 function to said subject.
A method of treating a subject having an inflammatory bowel, disease, comprising administering an effective amount of an antagonist of GPR-9-6 function to said subject.
A method of modulating a GPR-9-6 function comprising contacting a cell that expresses GPR-9-6 with an agent which binds thereto, thereby modulating the function of said GPR-9-6.
A test kit for use in detecting the presence of a mammalian GPR-9-6 or portion thereof in a biological sample comprising
- a) at least one antibody or antigen-binding fragment thereof which binds to a mammalian GPR-9-6 or portion of said receptor, wherein said antibody or antigen-binding fragment thereof inhibits binding of a ligand to the receptor;
- and
- b) one or more ancillary reagents suitable for detecting the presence of a complex between said antibody or antigen-binding fragment thereof and said mammalian GPR-9-6 or a portion thereof.
Dependencies are inferred from the claim text.