Methods and compositions for the diagnosis and treatment of demyelinating inflammatory disorders
AssigneesMillennium Pharmaceuticals, Inc., Robert Koch-Institutes
InventorsJames B. Rottman, Richard Kroczek
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Abstract
The present invention provides methods of suppressing demyelinating inflammatory disorders in a patient by administering to the patient a compound that inhibits binding of B7RP-1 to ICOS or inhibits signaling through the B7RP-1 pathway. Various therapeutic regimens are provided. Methods of identifying such compounds are also provided. The present invention further provides kits and pharmaceutical compositions useful in the present methods.
Claims26
A method of treating a multiple sclerosis in a patient, comprising administering to the patient in need of such treatment an ICOS-B7RP-1 inhibitor in an amount effective for treating the demyelinating inflammatory disorder, wherein the ICOS-B7RP-1 inhibitor is an anti-ICOS antibody.
A method of identifying a candidate ICOS-B7RP-1 inhibitor, comprising:
- (a) contacting an ICOS polypeptide with a B7RP-1 polypeptide expressed on an endothelial cell surface and a test compound, under conditions that, in the absence of the test compound, allow the ICOS polypeptide to bind to the B7RP-1 polypeptide and thereby form an ICOS-B7RP-1 complex;
- and
- (b) determining whether ICOS-B7RP-1 complex formation is inhibited by the test compound;
- wherein inhibition of ICOS-B7RP-1 complex formation by the test compound identifies the test compound as a candidate ICOS-B7RP-1 inhibitor.
A method of identifying a candidate ICOS-B7RP-1 inhibitor, comprising:
- (a) contacting a T-cell, capable of being activated by B7RP-1, with B7RP-1 present on an endothelial cell surface, in the presence of a test compound;
- and
- (b) determining whether a lower level of ICOS-B7RP-1 activity occurs in the T-cell after said contacting relative to a control T-cell contacted with B7RP-1 in the absence of the test compound;
- wherein a lower level of activity identifies the test compound as a candidate ICOS-B7RP-1 inhibitor.
A method of identifying a candidate ICOS-B7RP-1 inhibitor, comprising:
- (a) administering to a model animal with experimental allergic encephalomyelitis a test compound during the efferent stage of said experimental allergic encephalomyelitis;
- and
- (b) determining whether the test compound abrogates a central nervous system phenotype of experimental allergic encephalomyelitis,
- wherein abrogation of a central nervous system phenotype of experimental allergic encephalomyelitis identifies the test compound as a candidate ICOS-B7RP-1 inhibitor.
Dependencies are inferred from the claim text.