Antibodies that bind par-2

Abstract

The present invention provides compositions and methods relating to or derived from anti-PAR-2 antibodies. In particular embodiments, the invention provides antibodies that bind human PAR-2, PAR-2-binding fragments and derivatives of such antibodies, and PAR-2-binding polypeptides comprising such fragments. Other embodiments provide nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating or diagnosing subjects having PAR-2-related disorders or conditions.

What is claimed is: 
     
         1 . An isolated antigen binding protein, that binds to proteinase activated receptor-2 (PAR-2) and antagonizes the proteolytic activation thereof. 
     
     
         2 . The isolated antigen binding protein of  claim 1 , wherein the antigen binding protein antagonizes the proteolytic activation of PAR-2 with an IC50 of 60 nM or less in a fluorometric imaging plate reader (FLIPR) assay using HCT-116 cells. 
     
     
         3 . The isolated antigen binding protein of  claim 1  or  claim 2 , that specifically binds to the PAR-2 of a non-human primate, a cynomologous monkey, a chimpanzee, a non-primate mammal, a rodent, a mouse, a rat, a hamster, a guinea pig, a cat, or a dog. 
     
     
         4 . The isolated antigen binding protein of  claim 1  or  claim 2  wherein said antigen binding protein comprises:
 a. a human antibody; 
 b. a humanized antibody; 
 c. a chimeric antibody; 
 d. a monoclonal antibody; 
 e. a polyclonal antibody; 
 f. a recombinant antibody; 
 g. an antigen-binding antibody fragment; 
 h. a single chain antibody; 
 i. a diabody; 
 j. a triabody; 
 k. a tetrabody; 
 l. a Fab fragment; 
 m. a F(ab′) 2  fragment; 
 n. a domain antibody; 
 o. an IgD antibody; 
 p. an IgE antibody; 
 q. an IgM antibody; 
 r. an IgG1 antibody; 
 s. an IgG2 antibody; 
 t. an IgG3 antibody; 
 u. an IgG4 antibody; or 
 v. an IgG4 antibody having at least one mutation in a hinge region that alleviates a tendency to form intra-H chain disulfide bond. 
 
     
     
         5 . An isolated cell that secretes an antigen binding protein of  claim 1 , wherein the cell is a hybridoma. 
     
     
         6 . A method of making an antigen binding protein that binds PAR-2, comprising incubating the isolated cell of  claim 5  under conditions that allow it to express the antigen binding protein. 
     
     
         7 . A pharmaceutical composition comprising the antigen binding protein of  claim 1 . 
     
     
         8 . A method of treating a condition in a subject comprising administering to the subject the pharmaceutical composition of  claim 7 , wherein the condition is treatable by reducing the activity of PAR-2 in the subject. 
     
     
         9 . The method of  claim 8  wherein the subject is a human being. 
     
     
         10 . The method of  claim 9  wherein said condition is selected from the group consisting of inflammatory conditions of the skin, joints, gastrointestinal system and/or airway. 
     
     
         11 . A method of decreasing PAR-2 activity in a subject in need thereof comprising administering to the subject said pharmaceutical composition of  claim 7 . 
     
     
         12 . The method of  claim 11  wherein the PAR-2 activity that is decreased is PAR-2 signalling. 
     
     
         13 . The method of  claim 12 , wherein the PAR-2 signalling decrease results from inhibition of proteolytic activation of PAR-2.