Use following solution to clear content for specific range.
Microsoft.Office.Interop.Excel.Application excel = new Microsoft.Office.Interop.Excel.Application();
Microsoft.Office.Interop.Excel.Workbook excelWorkbook = excel.Workbooks.Open(@"D:\Book1.xls");
Microsoft.Office.Interop.Excel._Worksheet excelWorkbookWorksheet = excelWorkbook.Sheets[1];
var rng = excelWorkbookWorksheet.get_Range("B2:E4", Type.Missing);
rng.Cells.Clear();
excelWorkbook.Save();