Product and method for treatment of conditions associated with receptor-desensitization

Abstract

Particular members of the multisubunit immune recognition receptor (MIRR) family of receptors, specifically, the B cell antigen receptor (BCR), the pre-B cell receptor (pre-BCR), the pro-B cell receptor (pro-BCR), Ig Fc receptors (FcR), and NK receptors, can be physically uncoupled from their associated transducers. The invention describes regulatory compounds and methods for mimicking such dissociation/destabilization for the purposes of receptor desensitization and for treatment of conditions in which receptor desensitization or alternatively, enhanced or prolonged receptor sensitization, is desirable. Compounds and methods for enhancing or prolonging receptor sensitization are also disclosed, as are methods for identifying regulatory compounds suitable for use in the present methods.

1 . A method to desensitize an Ig Fc receptor, said method comprising: contacting an Ig Fc receptor, with a regulatory compound, wherein said receptor has a transducer component and an extracellular ligand binding component;
 wherein contact with said regulatory compound: (1) causes a dissociation of said extracellular ligand binding component from said transducer component when said components are associated with each other prior to contact with said compound; or (2) inhibits association of said extracellular ligand binding component with said transducer component when said components are dissociated from each other prior to contact with said compound.   
     
     
         2 - 49 . (canceled) 
     
     
         50 . The method of  claim 1 , wherein said regulatory compound binds to said extracellular ligand binding component. 
     
     
         51 . The method of  claim 1 , wherein said regulatory compound inhibits association of said extracellular ligand binding domain component with said transducer component when said components are dissociated from each other. 
     
     
         52 . The method of  claim 1 , wherein said transducer component is selected from the group consisting of FcRβ and FcRγ. 
     
     
         53 . The method of  claim 1 , wherein said receptor is a human Ig Fc receptor selected from the group consisting of FcαRI, FcεRI, FcγRI, FcγRIIa, FcγRIIb, FcγRIIc, FcγRIIIb, and wherein said regulatory compound selectively binds to an extracellular ligand binding domain of said Fc receptor. 
     
     
         54 . The method of  claim 53 , wherein said receptor comprises an alpha chain receptor extracellular binding component. 
     
     
         55 . The method of  claim 53 , wherein said receptor comprises an α chain receptor extracellular ligand binding component and a transducer component comprising a β chain and/or γ chain. 
     
     
         56 . The method of  claim 53 , wherein said receptor is expressed by a cell selected from the group consisting of a macrophage, a dendritic cell, a neutrophil, a mast cell and a basophil. 
     
     
         57 . The method of  claim 1 , wherein said regulatory compound is selected from the group consisting of an antibody, a peptide and a mimetope thereof. 
     
     
         58 . The method of  claim 1 , wherein said regulatory compound is an antibody 
     
     
         59 . The method of  claim 58 , wherein said antibody is monovalent. 
     
     
         60 . The method of  claim 58 , wherein said antibody is divalent. 
     
     
         61 . The method of  claim 57 , wherein said antibody binds to the extracellular ligand binding domain. 
     
     
         62 . The method of  claim 60 , wherein said antibody binds to the α chain receptor extracellular ligand binding component. 
     
     
         63 . The method of  claim 53 , wherein said regulatory compound is administered to a patient that has a condition associated with inflammation. 
     
     
         64 . The method of  claim 53 , wherein said condition is associated with allergic inflammation. 
     
     
         65 . The method of  claim 64 , wherein the condition associated with allergic inflammation is selected from the group consisting of allergic airway diseases, allergic rhinitis, allergic conjunctivitis and food allergy. 
     
     
         66 . The method of  claim 53 , wherein said regulatory compound is administered to a patient that has an autoimmune disease. 
     
     
         67 . The method of  claim 66 , wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, systemic lupus erythematosus, insulin dependent diabetes mellitis, multiple sclerosis, myasthenia gravis, Grave's disease, autoimmune hemolytic anemia, autoimmune thrombocytopenia purpura, Goodpasture's syndrome, pemphigus vulgaris, acute rheumatic fever, post-streptococcal glomerulonephritis, and polyarteritis nodosa. 
     
     
         68 . The method of  claim 1 , wherein said regulatory compound is administered to a patient by way of a therapeutic composition comprising a pharmaceutically acceptable carrier and said compound.