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, comprising administering an effective amount of a chemical compound inhibitor of the chitinase-like molecule to said mammal, thereby treating said inflammatory disease. 
     
     
         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, YKL-40, chitinase 3-like-1 and a chondrocyte protein 39. 
     
     
         45 . The method of  claim 42 , 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. 
     
     
         46 . 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. 
     
     
         47 . A method of preventing an inflammatory disease in a mammal, wherein said disease is associated with an increased level of a chitinase-like molecule, comprising administering an effective amount of a chemical compound inhibitor of the chitinase-like molecule to said mammal, thereby preventing said inflammatory disease. 
     
     
         48 . The method of  claim 47 , wherein said mammal is a human. 
     
     
         49 . The method of  claim 47 , wherein said chitinase-like molecule is selected from the group consisting of a YM-1, a YM-2, an AMCase, an oviductal glycoprotein 1, a cartilage glycoprotein 1, a chitotriosidase, a mucin 9, a cartilage glycoprotein-39, YKL-40, chitinase 3-like-1 and a chondrocyte protein 39. 
     
     
         50 . The method of  claim 47 , 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 . The method of  claim 47 , wherein said chemical compound 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. 
     
     
         52 . A method of treating an inflammatory disease in a mammal, wherein said disease is associated with an increased level of chitinase, comprising administering an effective amount of a chemical compound inhibitor of chitinase to said mammal, thereby treating said inflammatory disease. 
     
     
         53 . The method of  claim 52 , wherein said mammal is a human. 
     
     
         54 . The method of  claim 52 , wherein said chitinase is AMCase or chitotriosidase. 
     
     
         55 . The method of  claim 52 , wherein said chemical compound 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. 
     
     
         56 . The method of  claim 52 , 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. 
     
     
         57 . A method for treating an inflammatory disease in a mammal, wherein said disease is associated with an increased level of interleukin-13, comprising administering an effective amount of chemical compound inhibitor of a chitinase-like molecule to said mammal, thereby treating said inflammatory disease. 
     
     
         58 . The method of  claim 57 , wherein said mammal is a human. 
     
     
         59 . The method of  claim 57 , wherein said chitinase-like molecule is selected from the group consisting of a YM-1, a YM-2, an AMCase, an oviductal glycoprotein 1, a cartilage glycoprotein 1, a chitotriosidase, a mucin 9, a cartilage glycoprotein-39, YKL-40, chitinase 3-like-1 and a chondrocyte protein 39. 
     
     
         60 . The method of  claim 57 , wherein said inflammatory disease is selected from the group consisting of asthma and chronic obstructive pulmonary disease. 
     
     
         61 . The method of  claim 57 , wherein said chemical compound 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. 
     
     
         62 . A method for treating an inflammatory disease in a mammal, wherein said disease is associated with a Th2 inflammatory response, comprising administering an effective amount of a chemical compound inhibitor of a chitinase-like molecule to said mammal, thereby treating said inflammatory disease. 
     
     
         63 . The method of  claim 62 , wherein said mammal is a human. 
     
     
         64 . The method of  claim 62 , wherein said chitinase-like molecule is selected from the group consisting of a YM-1, a YM-2, an AMCase, an oviductal glycoprotein 1, a cartilage glycoprotein 1, a chitotriosidase, a mucin 9, a cartilage glycoprotein-39, YKL-40, chitinase 3-like-I and a chondrocyte protein 39. 
     
     
         65 . The method of  claim 62 , wherein inflammatory said 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. 
     
     
         66 . The method of  claim 62 , wherein said chemical compound 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. 
     
     
         67 . A method of inhibiting an activity of a chitinase-like molecule in a mammal, comprising administering an effective amount of a chemical compound inhibitor of the chitinase-like molecule to said mammal. 
     
     
         68 . The method of  claim 67 , wherein said mammal is suffering from an inflammatory disease associated with an increased level of a chitinase-like molecule. 
     
     
         69 . The method of  claim 68 , 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. 
     
     
         70 . The method of  claim 67 , wherein said mammal is a human. 
     
     
         71 . The method of  claim 67 , 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, YKL-40, chitinase 3-like-1 and a chondrocyte protein 39. 
     
     
         72 . The method of  claim 67 , wherein said chemical compound 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.