Methods, compositions and kits relating to chitinases and chitinase-like molecules and inflammatory disease

Abstract

The present invention includes compositions and methods for the treatment of inflammatory disease (e.g., asthma, COPD, inflammatory bowel disease, atopic dermatitis, atopy, allergy, allergic rhinitis, scleroderma, and the like), relating to inhibiting a chitinase-like molecule. The invention further includes methods to identify new compounds for the treatment of inflammatory disease, including, but not limited to, asthma, COPD and the like. This is because the present invention demonstrates, for the first time, that expression of IL-13, and of a chitinase-like molecule, mediates and/or is associated with inflammatory disease and that inhibiting the chitinase-like molecule treats and even prevents, the disease. Thus, the invention relates to the novel discovery that inhibiting a chitinase-like molecule treats and prevents an inflammatory disease.

1 - 41 . (canceled)  
     
     
         42 . A method of treating an inflammatory disease in a mammal wherein said disease is associated with an increased level of a chitinase-like molecule, said method comprising administering an effective amount of a chitinase-like molecule inhibitor to said mammal, thereby treating said inflammatory disease in said mammal.  
     
     
         43 . The method of  claim 42 , wherein said mammal is a human.  
     
     
         44 . The method of  claim 42 , wherein said chitinase-like molecule is selected from the group consisting of a YM-1, a YM-2, an acidic mammalian chitinase (AMCase), an oviductal glycoprotein 1, a cartilage glycoprotein 1, a chitotriosidase, a mucin 9, a cartilage glycoprotein-39, and a chondrocyte protein 39.  
     
     
         45 . The method of  claim 42 , wherein said chitinase-like molecule inhibitor is selected from the group consisting of a chemical compound, an antibody, a ribozyme, a nucleic acid, and an antisense nucleic acid molecule.  
     
     
         46 . The method of  claim 45 , wherein said chemical compound is selected from the group consisting of allosamidin, glucoallosamidin A, glucoallosamidin B, methyl-N-demethylallosamidin, demethylallosamidin, didemthylallosamidin, stylogaunidine, a styloguanidine derivative, dipeptide cyclo-(L-Arg-D-Pro), dipeptide cyclo-(L-Arg-L-Pro), dipeptide cyclo-(D-Arg-D-Pro), dipeptide cyclo-(D-Arg-L-Pro), riboflavin, a flavin derivative, copper, zinc, and mercury.  
     
     
         47 . The method of  claim 45 , wherein said antibody specifically binds with a chitinase-like molecule selected from the group consisting of a YM-1, a YM-2, an acidic mammalian chitinase (AMCase), an oviductal glycoprotein 1, a cartilage glycoprotein 1, a chitotriosidase, a mucin 9, a cartilage glycoprotein-39, and a chondrocyte protein 39.  
     
     
         48 . The method of  claim 45 , wherein said antisense nucleic acid molecule is an isolated nucleic acid complementary to an isolated nucleic acid encoding said chitinase-like molecule, or a fragment thereof.  
     
     
         49 . The method of  claim 45 , wherein said ribozyme is an isolated enzymatic nucleic acid, which specifically cleaves mRNA transcribed from a nucleic acid encoding said chitinase-like molecule.  
     
     
         50 . The method of  claim 42 , wherein said inflammatory disease is selected from the group consisting of asthma, chronic obstructive pulmonary disease, interstitial lung disease, chronic obstructive lung disease, chronic bronchitis, eosinophilic bronchitis, eosinophilic pneumonia, pneumonia, inflammatory bowel disease, atopic dermatitis, atopy, allergy, allergic rhinitis, idiopathic pulmonary fibrosis, scleroderma, and emphysema.  
     
     
         51 . A method of preventing an inflammatory disease in a mammal wherein said disease is associated with an increased level of a chitinase-like molecule, said method comprising administering an effective amount of a chitinase-like molecule inhibitor to said mammal, thereby preventing said inflammatory disease in said mammal.  
     
     
         52 . The method of  claim 51 , wherein said mammal is a human.  
     
     
         53 . The method of  claim 51 , wherein said chitinase-like molecule is selected from the group consisting of a YM-1, a YM-2, an acidic mammalian chitinase (AMCase), an oviductal glycoprotein 1, a cartilage glycoprotein 1, a chitotriosidase, a mucin 9, a cartilage glycoprotein-39, and a chondrocyte protein 39.  
     
     
         54 . The method of  claim 51 , wherein said chitinase-like molecule inhibitor is selected from the group consisting of a chemical compound, an antibody, a ribozyme, a nucleic acid, and an antisense nucleic acid molecule.  
     
     
         55 . The method of  claim 51 , wherein said inflammatory disease is selected from the group consisting of asthma, chronic obstructive pulmonary disease, interstitial lung disease, chronic obstructive lung disease, chronic bronchitis, eosinophilic bronchitis, eosinophilic pneumonia, pneumonia, inflammatory bowel disease, atopic dermatitis, atopy, allergy, allergic rhinitis, idiopathic pulmonary fibrosis, scleroderma, and emphysema.  
     
     
         56 . The method of  claim 51 , wherein said chitinase-like molecule is a YM protein and further wherein said chitinase-like molecule inhibitor is selected from the group consisting of allosamidin, glucoallosamidin A, glucoallosamidin B, methyl-N-demethylallosamidin, demethylallosamidin, didemthylallosamidin, styloguanidine, a styloguanidine derivative, dipeptide cyclo-(L-Arg-D-Pro), dipeptide cyclo-(L-Arg-L-Pro), dipeptide cyclo-(D-Arg-D-Pro), dipeptide cyclo-(D-Arg-L-Pro), riboflavin, a flavin derivative, copper, zinc, and mercury.  
     
     
         57 . The method of  claim 51 , wherein said chitinase-like molecule is AMCase.  
     
     
         58 . A method of treating an inflammatory disease in a mammal wherein said disease is associated with an increased level of chitinase, said method comprising administering an effective amount of a chitinase inhibitor to said mammal, thereby treating said inflammatory disease in said mammal.  
     
     
         59 . The method of  claim 58 , wherein said mammal is a human.  
     
     
         60 . The method of  claim 58 , wherein said chitinase is acidic mammalian chitinase (AMCase) and wherein said chitinase inhibitor is selected from the group consisting of a chemical compound, an antibody, a ribozyme, a nucleic acid, a nucleic acid, and an antisense nucleic acid molecule.  
     
     
         61 . The method of  claim 60 , wherein said chemical compound is selected from the group consisting of allosamidin, glucoallosamidin A, glucoallosamidin B, methyl-N- demethylallosamidin, demethylallosamidin, didemthylallosamidin, stylogaunidine, a styloguanidine derivative, dipeptide cyclo-(L-Arg-D-Pro), dipeptide cyclo-(L-Arg-L-Pro), dipeptide cyclo-(D-Arg-D-Pro), dipeptide cyclo-(D-Arg-L-Pro), riboflavin, a flavin derivative, copper, zinc, and mercury.  
     
     
         62 . The method of  claim 60 , wherein said antibody specifically binds with AMCase.  
     
     
         63 . The method of  claim 60 , wherein said antisense nucleic acid molecule is an isolated nucleic acid complementary to an isolated nucleic acid encoding an AMCase, or a fragment thereof.  
     
     
         64 . The method of  claim 58 , wherein said inflammatory disease is selected from the group consisting of asthma, chronic obstructive pulmonary disease, interstitial lung disease, chronic obstructive lung disease, chronic bronchitis, eosinophilic bronchitis, eosinophilic pneumonia, pneumonia, inflammatory bowel disease, atopic dermatitis, atopy, allergy, allergic rhinitis, idiopathic pulmonary fibrosis, scleroderma, and emphysema.  
     
     
         65 . A method for treating an inflammatory disease in a mammal wherein said disease is associated with an increased level of interleukin-13, said method comprising administering an effective amount of a chitinase-like molecule inhibitor to said mammal, thereby treating said inflammatory disease in a mammal.  
     
     
         66 . The method of  claim 65 , wherein said mammal is a human.  
     
     
         67 . The method of  claim 65 , wherein said chitinase-like molecule inhibitor is selected from the group consisting of a chemical compound, an antibody, a ribozyme, a nucleic acid, and an antisense nucleic acid molecule.  
     
     
         68 . A method for treating an inflammatory disease in a mammal wherein said disease is associated with a Th2 inflammatory response, said method comprising administering an effective amount of a chitinase-like molecule inhibitor to said mammal, thereby treating said inflammatory disease in a mammal.  
     
     
         69 . A method of identifying a compound useful for treating an inflammatory disease in a mammal, said method comprising administering a compound to a mammal afflicted with an inflammatory disease and comparing the level of a chitinase-like molecule in said mammal with the level of said chitinase-like molecule in said mammal prior to administration of said compound, wherein a lower level of said chitinase-like molecule in said mammal after administration of said compound compared with said level of said chitinase-like molecule in said mammal prior to administration of said compound is an indication that said compound is useful for treating an inflammatory disease in said mammal, thereby identifying a compound useful for treating an inflammatory disease.  
     
     
         70 . The method of  claim 69 , wherein said level of a chitinase-like molecule is selected from the group consisting of the level of chitinase-like molecule nucleic acid expression and the level of chitinase-like molecule enzymatic activity.  
     
     
         71 . The method of  claim 69 , wherein said chitinase-like molecule is selected from the group consisting of a YM-1, a YM-2, an Acidic Mammalian Chitinase (AMCase), an oviductal glycoprotein 1, a cartilage glycoprotein 1, a chitotriosidase, a mucin 9, a cartilage glycoprotein-39, and a chondrocyte protein 39.  
     
     
         72 . The method of  claim 69 , wherein said mammal is a mouse.  
     
     
         73 . The method of  claim 72 , wherein said mouse is selected from the group consisting of a transgenic mouse constitutively expressing interleukin 13 and a transgenic mouse inducibly expressing interleukin 13.  
     
     
         74 . A compound identified using the method of  claim 69 .  
     
     
         75 . The method of  claim 69 , wherein said chitinase-like molecule is AMCase.  
     
     
         76 . A compound identified using the method of  claim 75 .  
     
     
         77 . A method of identifying a compound useful for treating an inflammatory disease, said method comprising contacting a cell with a compound and comparing the level of a chitinase-like molecule in said cell with the level of said chitinase-like molecule in an otherwise identical cell not contacted with said compound, wherein a lower level of said chitinase-like molecule in said cell contacted with said compound compared with said level of said chitinase-like molecule in said cell not contacted with said compound is an indication that said compound is useful for treating an inflammatory disease, thereby identifying a compound useful for treating an inflammatory disease.  
     
     
         78 . A kit for treating an inflammatory disease in a mammal wherein said disease is associated with an increased level of a chitinase-like molecule, said kit comprising an effective amount of a chitinase-like molecule inhibitor, said kit further comprising an applicator and an instructional material for the use thereof.  
     
     
         79 . The kit of  claim 78 , wherein said chitinase-like molecule inhibitor is selected from the group consisting of a chemical compound, an antibody, a ribozyme, an antisense molecule, and a nucleic acid.  
     
     
         80 . The kit of  claim 79 , wherein said chemical compound is selected from the group consisting of allosamidin, glucoallosamidin A, glucoallosamidin B, methyl-N-demethylallosamidin, demethylallosamidin, didemthylallosamidin, stylogaunidine, a styloguanidine derivative, dipeptide cyclo-(L-Arg-D-Pro), dipeptide cyclo-(L-Arg-L-Pro), dipeptide cyclo-(D-Arg-D-Pro), dipeptide cyclo-(D-Arg-L-Pro), riboflavin, a flavin derivative, copper, zinc, and mercury.  
     
     
         81 . The kit of  claim 80 , wherein said chitinase-like molecule is AMCase.  
     
     
         82 . A kit for preventing an inflammatory disease in a mammal wherein said disease is associated with an increased level of a chitinase-like molecule, said kit comprising an effective amount of an chitinase-like molecule inhibitor, said kit further comprising an applicator and an instructional material for the use thereof.