5.1 and up

- (BOOL)addSkipBackupAttributeToItemAtURL:(NSURL *)URL
{
    assert([[NSFileManager defaultManager] fileExistsAtPath: [URL path]]);
 
    NSError *error = nil;
    BOOL success = [URL setResourceValue: [NSNumber numberWithBool: YES]
                                  forKey: NSURLIsExcludedFromBackupKey error: &error];
    if(!success){
        NSLog(@"Error excluding %@ from backup %@", [URL lastPathComponent], error);
    }
    return success;
}

5.0.1

#import 
- (BOOL)addSkipBackupAttributeToItemAtURL:(NSURL *)URL
{
    assert([[NSFileManager defaultManager] fileExistsAtPath: [URL path]]);
 
    const char* filePath = [[URL path] fileSystemRepresentation];
 
    const char* attrName = "com.apple.MobileBackup";
    u_int8_t attrValue = 1;
 
    int result = setxattr(filePath, attrName, &attrValue, sizeof(attrValue), 0, 0);
    return result == 0;
}

Source