Egfr antagonist for the treatment of heart disease

Abstract

The present invention relates to the use of epidermal growth factor receptor (EGFR) antagonists in methods and compositions useful for the treatment of heart disease in a subject. In one embodiment, the methods of the present invention comprise: (a) administering to the subject an EGFR antagonist; and (b) inhibiting or substantially inhibiting the EGFR signal transduction cascade. In another embodiment the method of the present invention may be used in combination with another heart disease therapy.

1 - 42 . (canceled) 
     
     
         43 . A method for the treatment of heart disease in a subject comprising administering to the subject an epidermal growth factor receptor (EGFR) antagonist. 
     
     
         44 . The method of  claim 43  wherein said subject is also being administered at least one other heart disease therapy. 
     
     
         45 . The method of  claim 44  wherein the at least one other heart disease therapy includes small-molecule drugs, complement inhibitors, beta blockers, angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), aldosterone antagonists, thrombolylic therapy, mechanical cardiac reperfusion or any combinations thereof. 
     
     
         46 . The method of  claim 43  wherein heart disease includes acute myocardial infarction, myocardial infarction, heart failure, systolic or diastolic heart failure, heart failure due to hypertension or diabetes, cardiomyopathy, ischemic cardiomyopathy or hypertrophic cardiomyopathy. 
     
     
         47 . The method of  claim 43  wherein heart disease is myocardial infarction, and wherein the EGFR antagonist is provided to the subject following the myocardial infarction. 
     
     
         48 . The method of  claim 43  wherein the treatment includes treating preventing or minimizing complications associated with heart disease, the complications selected from the group consisting of: cardiac hypertrophy, maladaptive myocardial remodeling, long term cardiac remodeling, heart scar healing and cardiac rupture. 
     
     
         49 . The method of  claim 43  wherein the subject is deficient in a tissue inhibitor of matrix metalloproteinase (TIMP). 
     
     
         50 . The method of  claim 49  wherein the TIMP is TIMP3. 
     
     
         51 . The method of  claim 43  wherein the EGFR antagonist is an EGFR ligand variant capable of inhibiting at least one EGFR-mediated biological activity. 
     
     
         52 . The method of  claim 43  wherein the EGFR antagonist is selected from the group consisting of an anti-EGFR antibody, an anti-EGFR antibody fragment, an anti-EGFR ligand antibody or an anti-EGFR ligand antibody fragment. 
     
     
         53 . The method of  claim 43  wherein the EGFR antagonist is selected from the group consisting of cetuximab, pinitumumab, bevacizumab, zalutumumab, nimotuzumab or matuzumab. 
     
     
         54 . The method of  claim 43  wherein the EGFR antagonist is selected from the group consisting of erlotinib, gefitinib, PD-183805. PD169540, PD-158780, AG1478, PD153035, CGP59326, PKI166, EKB569, or GW572016. 
     
     
         55 . The method of  claim 43  wherein the EGFR antagonist is a siRNA, a miRNA, a ribozyme, or an antisense oligonucleotide. 
     
     
         56 . The method of  claim 43  wherein the EGFR antagonist is administered to the subject by injection. 
     
     
         57 . The method of  claim 43  wherein the EGFR antagonist is administered to the subject by liposome delivery. 
     
     
         58 . The method of  claim 43  wherein the EGFR antagonist is administered to the subject via an implantable device capable of sustained release of the EGFR antagonist. 
     
     
         59 . A method of treating scar healing in a subject, said method comprising administering the subject an effective amount of an EGFR antagonist. 
     
     
         60 . The method of  claim 59  wherein said method is a method of minimizing maladaptive cardiac remodeling. 
     
     
         61 . The method of  claim 59  wherein the subject is deficient in a tissue inhibitor of matrix metalloproteinase (TIMP). 
     
     
         62 . The method of  claim 61  wherein the TIMP is TIMP3. 
     
     
         63 . The method of  claim 59  wherein the EGFR antagonist is an EGFR ligand variant capable of inhibiting at least one EGFR-mediated biological activity. 
     
     
         64 . The method of  claim 59  wherein the EGFR antagonist is selected from the group consisting of an anti-EGFR antibody, an EGFR antibody fragment, an anti-EGFR ligand antibody or an anti-EGFR ligand antibody fragment. 
     
     
         65 . The method of  claim 59  wherein the EGFR antagon is selected from the group consisting of cetuximab, pinitumumab, bevacizumab, zalutumumab, nimotuzumab or matuzumab. 
     
     
         66 . The method of  claim 59  wherein the EGFR antagonist is selected from the group consisting of erlotinib, gefitinib, PD183805, PD169540, PD-158780. AG1478, PD153035, CGP59326, PKI166, EKB569, or GW572016. 
     
     
         67 . The method of  claim 59  wherein the EGFR antagonist is a siRNA, a miRNA, a ribozyme, or an antisense oligonucleotide. 
     
     
         68 . The method of  claim 59  wherein the EGFR antagonist is administered to the subject by injection. 
     
     
         69 . The method of  claim 59  wherein the EGFR antagonist is administered to the subject by liposome delivery. 
     
     
         70 . The method of  claim 59  wherein the EGFR antagonist is administered to the subject via an implantable device capable of sustained release of the EGFR antagonist.